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Mak JWY, Law AWH, Law KWT, Ho R, Cheung CKM, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol 2023; 29:4942-4961. [PMID: 37731995 PMCID: PMC10507505 DOI: 10.3748/wjg.v29.i33.4942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/22/2023] [Accepted: 08/15/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | | | | | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong 852, China
| | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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2
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Teh BW, Reynolds G, Slavin MA, Cooley L, Roberts M, Liu E, Thursky K, Talaulikar D, Mollee P, Szabo F, Ward C, Chan H, Prince HM, Harrison SJ. Executive summary of consensus clinical practice guidelines for the prevention of infection in patients with multiple myeloma. Intern Med J 2023; 53:1469-1477. [PMID: 37093163 DOI: 10.1111/imj.16100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 04/10/2023] [Indexed: 04/25/2023]
Abstract
Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.
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Affiliation(s)
- Benjamin W Teh
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Gemma Reynolds
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Infectious Diseases, Austin Health, Melbourne, Victoria, Australia
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Louise Cooley
- Department of Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Matthew Roberts
- Department of Infectious Diseases, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Eunice Liu
- Department of Infectious Diseases, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Karin Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - Dipti Talaulikar
- Department of Haematology, Canberra Hospital, Canberra, Australian Capital Territory, Australia
- College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Peter Mollee
- Queensland Haematology Department, Princess Alexandra Hospital, Sydney, Queensland, Australia
- School of Medicine, University of Queensland, Sydney, Queensland, Australia
| | - Ferenc Szabo
- Haematology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia
- Menzies School of Health Research, Darwin, Northern Territory, Australia
- Flinders University, Adelaide, South Australia, Australia
| | - Chris Ward
- Department of Haematology, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Kolling Institute, University of Sydney, Sydney, New South Wales, Australia
| | - Henry Chan
- Department of Haematology, Waitemata District Health Board, Auckland, New Zealand
- Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - H Miles Prince
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
- Epworth Healthcare, Melbourne, Victoria, Australia
| | - Simon J Harrison
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
- Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia
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Mizuno S, Takami A, Takamatsu H, Hanamura I, Shimazu Y, Hangaishi A, Tsukada N, Kako S, Kikuchi T, Ota S, Shimizu H, Iida S, Yoshioka S, Sawa M, Fukuda T, Kanda Y, Atsuta Y, Kawamura K. Autologous hematopoietic cell transplantation for myeloma patients with hepatitis B virus or hepatitis C virus in the era of novel agents. Bone Marrow Transplant 2022; 57:846-848. [PMID: 35332303 DOI: 10.1038/s41409-022-01640-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/09/2022]
Affiliation(s)
- Shohei Mizuno
- Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
| | - Akiyoshi Takami
- Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Hiroyuki Takamatsu
- Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences/ Faculty of Transdisciplinary Sciences, Institute of Transdisciplinary Sciences, Kanazawa University, Kanazawa, Japan
| | - Ichiro Hanamura
- Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yutaka Shimazu
- Department of Hematology, Kyoto University Hospital, Kyoto, Japan
| | - Akira Hangaishi
- Department of Hematology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Nobuhiro Tsukada
- Division of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Shinichi Kako
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Taku Kikuchi
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shuichi Ota
- Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan
| | - Hiroaki Shimizu
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Hospital, Nagoya, Japan
| | - Satoshi Yoshioka
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Takahiro Fukuda
- Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshinobu Kanda
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan.,Division of Hematology, Jichi Medical University, Shimotsuke, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.,Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Koji Kawamura
- Department of Hematology, Tottori University Hospital, Yonago, Japan
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Shih CA, Chen WC. Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy. World J Clin Cases 2021; 9:5769-5781. [PMID: 34368296 PMCID: PMC8316946 DOI: 10.12998/wjcc.v9.i21.5769] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/12/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
- Department of Nursing, Meiho University, Pingtung County 928, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung 8424, Taiwan
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Zhang X, Liang Y, Li X, Wang W, Tong J, Xu Y. Clearance of HBsAg in a patient with familial multiple myeloma after a bortezomib-based regimen combined with anti-HBV drug: A case report. Medicine (Baltimore) 2020; 99:e22642. [PMID: 33019490 PMCID: PMC7535632 DOI: 10.1097/md.0000000000022642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 07/18/2020] [Accepted: 09/09/2020] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.
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Affiliation(s)
- Xuzhao Zhang
- Department of Hematology
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management. Viruses 2019; 11:v11090858. [PMID: 31540124 PMCID: PMC6784078 DOI: 10.3390/v11090858] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 09/10/2019] [Accepted: 09/12/2019] [Indexed: 12/12/2022] Open
Abstract
It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs.
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Ataca Atilla P, Yalçıner M, Atilla E, İdilman R, Beksaç M. Hepatitis B Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Regimens Containing Lenalidomide and/or Bortezomib. Turk J Haematol 2019; 36:266-273. [PMID: 31368290 PMCID: PMC6863023 DOI: 10.4274/tjh.galenos.2019.2019.0103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective: Reactivation of the hepatitis B virus (HBV) refers to an increase in HBV replication in a patient with inactive or resolved HBV. In this retrospective study, our aim is to present and compare HBV reactivation in multiple myeloma (MM) patients who received lenalidomide and/or bortezomib at any time during treatment, evaluate the factors associated with reactivation, and demonstrate the outcome of patients. Materials and Methods: We evaluated 178 MM patients who received lenalidomide (n=102) and/or bortezomib (n=174) during their treatment schedules. The HBsAg, anti-HBc, anti-HBs, HBeAg, and anti-HBe were detected by chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers were determined by quantitative PCR. The results were evaluated by IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). Results: HBV reactivation was diagnosed in 6 patients (3%) after bortezomib and in 8 patients (8%) after bortezomib and lenalidomide. Three of the patients in each group had HBsAg+, HBeAg+, AntiHBeAg-, AntiHBc-, and AntiHBS+ status, whereas 5 patients in the bortezomib- and lenalidomide-treated group and 3 patients in the bortezomib-treated group had HBsAg-, HBeAg-, AntiHBeAg-, AntiHBc-, and AntiHBS+ status prior to treatment. There were no statistical differences observed between HBV reactivation in the bortezomib-treated or bortezomib- and lenalidomide-treated groups in terms of age at diagnosis, sex, International Staging System subtype, frequency of extramedullary disease, dialysis requirement, or receiving of autologous stem cell transplantation. In patients who received antiviral prophylaxis, a higher incidence of HBV reactivation was detected in HBsAg-positive patients compared to HBsAg-negative patients (4/4, 100% vs. 2/7, 29%; p=0.045). The 3-year and 5-year overall survival rates were similar in patients with or without HBV reactivation (83% vs. 84%, 73% vs. 74%, p=0.84). Conclusion: Close follow-up is recommended for not only HBsAg-positive but also HBsAg-negative patients.
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Affiliation(s)
- Pınar Ataca Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Merih Yalçıner
- Ankara University Faculty of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Erden Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Ramazan İdilman
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Meral Beksaç
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
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Girmenia C, Cavo M, Offidani M, Scaglione F, Corso A, Di Raimondo F, Musto P, Petrucci MT, Barosi G. Management of infectious complications in multiple myeloma patients: Expert panel consensus-based recommendations. Blood Rev 2019; 34:84-94. [PMID: 30683446 DOI: 10.1016/j.blre.2019.01.001] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 12/22/2018] [Accepted: 01/08/2019] [Indexed: 02/08/2023]
Abstract
The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunoregulatory drugs and monoclonal antibodies, has improved the outcomes of patients, but in parallel has changed the frequency and epidemiology of infections. Hence, the great strides in the indications and use of new active treatments for MM need parallel progresses on the best approach to prophylaxis and supportive therapy for infections. Moving from the recognition that the above issue represents an unmet clinical need in MM, an expert panel assessed the scientific literature and composed a framework of recommendations for optimal infection control in patients candidate to active treatment for MM. The present publication represents a consensus document from questionnaires and consensus meetings held during 2017. The issues tackled in the project dealt with: infectious risk assessment, risk management and prophylaxis, intravenous immunoglobulin replacement therapy, antiviral and antibacterial vaccination. Considering the lack of conclusive and/or enough large studies for certain topics several recommendations derived from the personal experience of the experts.
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Affiliation(s)
- Corrado Girmenia
- Dipartimento di Ematologia, Oncologia, e Dermatologia, Azienda Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
| | - Michele Cavo
- 'Seràgnoli' Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
| | - Massimo Offidani
- Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy
| | - Francesco Scaglione
- Department of Oncology and Hemato-oncology, Università degli Studi di Milano, Milan, Italy
| | - Alessandro Corso
- Division of Hematology, Fondazione IRCCS - Policlinico San Matteo, Pavia, Italy
| | - Francesco Di Raimondo
- Division of Hematology, Azienda Policlinico-Vittorio Emanuele-Catania, and Department of Biomedicine and Molecular Medicine, University of Catania, Catania, Italy
| | - Pellegrino Musto
- Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy
| | - Maria Teresa Petrucci
- Dipartimento di Ematologia, Oncologia, e Dermatologia, Azienda Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Giovanni Barosi
- Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
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9
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Sanagawa A, Hotta Y, Kataoka T, Maeda Y, Kondo M, Kawade Y, Ogawa Y, Nishikawa R, Tohkin M, Kimura K. Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System. Cancer Med 2018; 7:2269-2279. [PMID: 29663729 PMCID: PMC6010750 DOI: 10.1002/cam4.1429] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 01/14/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.
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Affiliation(s)
- Akimasa Sanagawa
- Department of PharmacyNagoya City University HospitalNagoyaJapan
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Yuji Hotta
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Tomoya Kataoka
- Department of Clinical PharmaceuticsGraduate School of Medical SciencesNagoya City UniversityNagoyaJapan
| | - Yasuhiro Maeda
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Masahiro Kondo
- Department of PharmacyNagoya City University HospitalNagoyaJapan
| | - Yoshihiro Kawade
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Yoshihiro Ogawa
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Ryohei Nishikawa
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Masahiro Tohkin
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Kazunori Kimura
- Department of PharmacyNagoya City University HospitalNagoyaJapan
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
- Department of Clinical PharmaceuticsGraduate School of Medical SciencesNagoya City UniversityNagoyaJapan
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10
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Chen CY, Tien FM, Cheng A, Huang SY, Chou WC, Yao M, Tang JL, Tien HF, Sheng WH. Hepatitis B reactivation among 1962 patients with hematological malignancy in Taiwan. BMC Gastroenterol 2018; 18:6. [PMID: 29310589 PMCID: PMC5759199 DOI: 10.1186/s12876-017-0735-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 12/22/2017] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND The risk of Hepatitis B virus (HBV) reactivation in patients with different hematological malignancy except lymphoma were rarely known before. METHODS A total of 1962 patients with hematological malignancy were enrolled and followed-up at the National Taiwan University Hospital between 2008 and 2013. The clinical characteristics, HBV serology, and laboratory data were retrospectively reviewed and analyzed. RESULTS A total of 1962 patients comprising 1048 men and 914 women were studied. The median age of the patients was 55 years (range, 15-97 years). Chronic HBV carriage was documented at diagnosis of hematological malignancy in 286 (14.6%) patients. A total of 171 (59.8%) of the 286 HBV carriers received primary prophylaxis with anti-HBV agents. Of the HBV carriers, 97 (33.9%) developed hepatitis B reactivation during or after chemotherapy, including 59 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among patients with hematological malignancy and HBV carriage was 10.4 per 100 person-years. A multivariate analysis revealed hepatocellular carcinoma (p < 0.001) and antiviral prophylaxis use (p < 0.001) were independent risk factors of HBV reactivation in HBV carriers. Of the 1676 patients with initial negative hepatitis B surface antigen (HBsAg) counts, 41 (2.4%) experienced hepatitis B reactivation, reverse seroconversion of HBsAg, and lost their protective hepatitis B surface antibody (anti-HBs). A multivariate analysis revealed that diabetes mellitus (p = 0.005, odds ratio (OR): 0.218, 95% confidence interval (CI): 0.076-0.629), allogeneic transplantation (p = 0.013, OR: 0.182, 95% CI: 0.047-0.701), liver cirrhosis (p < 0.001, OR: 0.002, 95% CI: 0-0.047), low anti-HBs titers (p = 0.016, OR: 0.020, 95% CI: 0.001-0.480), and positive hepatitis B core antibody (p = 0.013, OR: 0.070, 95% CI: 0.009-0.571) were independent risk factors of positive seroconversion of HBsAg in patients with hematological malignancy. CONCLUSIONS The incidence of HBV reactivation among the patients with varying subtypes of hematological malignancy is similar. Prophylaxis with anti-HBV agents critically reduced the risk of hepatitis B reactivation.
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Affiliation(s)
- Chien-Yuan Chen
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Feng-Ming Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Aristine Cheng
- Division of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Shang-Yi Huang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Chien Chou
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming Yao
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jih-Luh Tang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Tai-Cheng Stem Cell Therapy Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hwei-Fang Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wang-Huei Sheng
- Division of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
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11
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Infectious complications in multiple myeloma receiving autologous stem cell transplantation in the past 10 years. Int J Hematol 2017; 106:801-810. [PMID: 28825207 DOI: 10.1007/s12185-017-2313-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 08/05/2017] [Accepted: 08/07/2017] [Indexed: 12/23/2022]
Abstract
Infection is one of the main causes of early-treatment mortality in multiple myeloma (MM) patients during autologous stem cell transplantation (autoSCT). In the present study, we sought to determine the incidence of, and risk factors for, infection during hospital stays after autoSCT. We retrospectively evaluated 324 autoSCT events that occurred in 285 MM patients between 2006 and 2015, and reviewed the clinical characteristics of patients and history of infections. Sixty-eight infection events occurred, including bacteremia (24), other bacterial infections (7), as well as infections caused by Cytomegalovirus (17), Herpes simplex virus (12), Varicella zoster virus (3), Aspergillus (3) and Pneumocystis jiroveci (2). There was no significant difference in number of infections in the 2006-2010 and 2011-2015 periods (P = 0.194). Risk factors for bacteremia included higher beta-2 microglobulin levels at diagnosis [≥3.5 mg/L; adjusted odds ratio (aOR) 3.544 (95% CI 1.070-11.736), P = 0.038] and previous bortezomib treatment [aOR 4.270 (95% CI 1.389-13.125), P = 0.011]. In-hospital mortality occurred in 1.2% of all cases and all were infection-related. In conclusion, infection was the main cause of in-hospital mortality in patients who underwent autoSCT. Bacteremia was the most common type of microbiologically confirmed infection, and was associated with higher beta-2 microglobulin levels and previous bortezomib treatment.
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12
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Gentile G, Andreoni M, Antonelli G, Sarmati L. Screening, monitoring, prevention, prophylaxis and therapy for hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation: a systematic review. Clin Microbiol Infect 2017; 23:916-923. [PMID: 28668465 DOI: 10.1016/j.cmi.2017.06.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/15/2017] [Accepted: 06/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The growth of new therapeutic options and practices increases the risk of hepatitis B virus (HBV) reactivation in patients with haematologic malignancies and/or patients undergoing haematologic stem cell transplantation (HSCT). OBJECTIVES To provide a systematic review supporting recommendations for prevention, monitoring, prophylaxis and therapy of HBV reactivation in patients with haematologic malignancies and HSCT. DATA SOURCES The systematic review was based on a strategy using PubMed and the Cochrane Library searching literature published from 1991 to December 31, 2016. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed. SELECTION CRITERIA Randomized control trials, prospective and retrospective cohort studies. RISK-OF-BIAS ASSESSMENT Cochrane Risk of Bias Tool and Newcastle Ottawa Quality Assessment Scale. RESULTS Forty-two studies of fair or good quality were included in this systematic review. The following main results were obtained: haematologic patients should be screened for HBV before chemotherapy; HBV DNA levels should be monthly monitored in all HBV-positive patients not receiving prophylaxis; hepatitis B surface antigen (HBsAg)-positive haematologic patients and patients undergoing HSCT should receive prophylaxis and third-generation HBV drugs should be provided; and anti-hepatitis B core protein-positive lymphoma patients and patients who underwent HSCT should receive antiviral prophylaxis. CONCLUSIONS A higher quality of evidence is needed. However, the level of evidence was sufficient to support the recommendations published in this issue of the journal.
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Affiliation(s)
- G Gentile
- Department of Cellular Biotechnologies and Haematology, La Sapienza University, Rome, Italy
| | - M Andreoni
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy
| | - G Antonelli
- Department of Molecular Medicine, La Sapienza University, Rome, Italy
| | - L Sarmati
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy.
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13
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Zhang MY, Zhu GQ, Zheng JN, Cheng Z, Van Poucke S, Shi KQ, Huang HH, Chen FY, Zheng MH. Nucleos(t)ide analogues for preventing HBV reactivation in immunosuppressed patients with hematological malignancies: a network meta-analysis. Expert Rev Anti Infect Ther 2017; 15:503-513. [PMID: 28317397 DOI: 10.1080/14787210.2017.1309291] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 03/17/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND We aimed to evaluate the efficacy of five oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of hepatitis B virus (HBV) reactivation and HBV-related complications in chronic hepatitis B virus (CHB) infected patients with hematological malignancies receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) by network meta-analysis. METHODS The search identified 28 articles involving 5 different prophylactic regimens covering 1478 participants. RESULTS Among five prophylactic regimes, tenofovir (predicted probability, 90%), was the most effective intervention followed by entecavir (88%) in preventing HBV reactivation. There was no significant difference between tenofovir and entecavir for preventing HBV reactivation. With regards to other outcomes, tenofovir and telbivudine was not included to evaluate due to lack of relevant studies. Entecavir was the most effective intervention in reducing the risk of HBV related hepatitis (100%), HBV related death (61%) and all other causes of hepatitis (98%). CONCLUSION Tenofovir and entecavir might be the most potent regimes in prevention of HBV reactivation for CHB infected patients with hematological malignancies undergoing chemotherapy or HSCT.
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Affiliation(s)
- Min-Yue Zhang
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Gui-Qi Zhu
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Ji-Na Zheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Zhang Cheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- d Department of Anesthesiology , Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Ke-Qing Shi
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- e Institute of Hepatology, Wenzhou Medical University , Wenzhou , China
| | - Hong-Hui Huang
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Fang-Yuan Chen
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Ming-Hua Zheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- e Institute of Hepatology, Wenzhou Medical University , Wenzhou , China
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14
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Varma A, Biritxinaga L, Saliba RM, Stich M, Jauch SF, Afrough A, Honhar M, Popat UR, Shafi MA, Shah N, Bashir Q, Dinh Y, Hosing C, Champlin RE, Qazilbash MH. Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant 2017; 23:581-587. [PMID: 28063964 PMCID: PMC5749257 DOI: 10.1016/j.bbmt.2017.01.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 01/01/2017] [Indexed: 01/01/2023]
Abstract
Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.
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Affiliation(s)
- Ankur Varma
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas
| | - Laura Biritxinaga
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rima M Saliba
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Maximilian Stich
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sarah Francesca Jauch
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Aimaz Afrough
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Medhavi Honhar
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Uday R Popat
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mehnaz A Shafi
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Nina Shah
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Qaiser Bashir
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yvonne Dinh
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Chitra Hosing
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Richard E Champlin
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Muzaffar H Qazilbash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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15
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Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant. Case Reports Hepatol 2017; 2017:2463953. [PMID: 28428898 PMCID: PMC5385905 DOI: 10.1155/2017/2463953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 03/06/2017] [Indexed: 01/25/2023] Open
Abstract
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.
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16
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Lu J, Chen WM, Geng CY, Durie BG, Huang XJ. Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study. Chin Med J (Engl) 2017; 129:274-8. [PMID: 26831227 PMCID: PMC4799569 DOI: 10.4103/0366-6999.174508] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Background: The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. Methods: From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. Results: The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). Conclusions: Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.
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Affiliation(s)
| | | | | | | | - Xiao-Jun Huang
- Department of Hematology, Peking University People's Hospital and Peking University Institute of Hematology, Beijing 100044, China
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17
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Li Y, Bai O, Liu C, Du Z, Wang X, Wang G, Li W. Association between hepatitis B virus infection and risk of multiple myeloma: a systematic review and meta-analysis. Intern Med J 2016; 46:307-14. [PMID: 26662071 DOI: 10.1111/imj.12981] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 08/02/2015] [Accepted: 12/03/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a major global public health concern. Although recent findings suggest an inverse relationship between HBV infection and multiple myeloma (MM), the true relationship between these two conditions remains unclear. AIM The primary aim of this meta-analysis was to evaluate the association between HBV infection, defined as hepatitis B surface antigen positivity, and the incidence of MM. METHODS We searched the PubMed/Medline, Cochrane Library and EMBASE databases from January 1975 to July 2014 and reviewed the reference lists of all retrieved articles. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed- and random-effects models. RESULTS We identified nine case-control studies involving 30,646 patients with MM and 379,837 controls. HBV infection was not significantly associated with the development of MM (OR = 1.3; 95% CI: 0.92-1.82; P = 0.14). A similar risk of developing MM was present in different HBV-prevalent countries. However, significant heterogeneity was observed among studies (P = 0.01). A statistically significant relationship between HBV infection and increased MM risk was detected in sub-analyses evaluating high-quality studies and those with hospital-based controls (P < 0.05). CONCLUSION HBV infection may be associated with an increased risk of MM. However, confirmation of this relationship and the specific molecular mechanisms involved in the association between HBV infection and the development of MM require further exploration.
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Affiliation(s)
- Y Li
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - O Bai
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - C Liu
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Z Du
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - X Wang
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - G Wang
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - W Li
- Cancer Center, First Hospital of Jilin University, Changchun, Jilin Province, China
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18
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Law MF, Ho R, Cheung CKM, Tam LHP, Ma K, So KCY, Ip B, So J, Lai J, Ng J, Tam THC. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol 2016; 22:6484-6500. [PMID: 27605883 PMCID: PMC4968128 DOI: 10.3748/wjg.v22.i28.6484] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/24/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
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19
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Tsukune Y, Sasaki M, Odajima T, Isoda A, Matsumoto M, Koike M, Tamura H, Moriya K, Ito S, Asahi M, Imai Y, Tanaka J, Handa H, Koiso H, Tanosaki S, Hua J, Hagihara M, Yahata Y, Suzuki S, Watanabe S, Sugimori H, Komatsu N. Incidence and clinical background of hepatitis B virus reactivation in multiple myeloma in novel agents' era. Ann Hematol 2016; 95:1465-72. [PMID: 27358178 DOI: 10.1007/s00277-016-2742-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 06/24/2016] [Indexed: 01/16/2023]
Abstract
There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients.
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Affiliation(s)
- Yutaka Tsukune
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Makoto Sasaki
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Takeshi Odajima
- Faculty of Health Science, Daito Bunka University School of Sports and Health Science, Saitama, Japan
| | - Atsushi Isoda
- Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan
| | - Morio Matsumoto
- Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan
| | - Michiaki Koike
- Department of Hematology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Hideto Tamura
- Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
| | - Keiichi Moriya
- Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
| | - Shigeki Ito
- Department of Medical Oncology, Iwate Medical University School of Medicine, Iwate, Japan
| | - Maki Asahi
- Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan
| | - Yoichi Imai
- Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junji Tanaka
- Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroshi Handa
- Department of Medicine and Clinical Science, Gunma University, Gunma, Japan
| | - Hiromi Koiso
- Infection Control and Prevention Center, Gunma University Hospital, Gunma, Japan
| | - Sakae Tanosaki
- Department of Hematology, The Fraternity Memorial Hospital, Tokyo, Japan
| | - Jian Hua
- Department of Hematology, Eiju General Hospital, Tokyo, Japan
| | - Masao Hagihara
- Department of Hematology, Eiju General Hospital, Tokyo, Japan
| | - Yuriko Yahata
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Satoko Suzuki
- Department of Gastroenterology, Tokyo Metropolitan Health and Medical Treatment Corporation Tobu Chiiki Hospital, Tokyo, Japan
| | - Sumio Watanabe
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroki Sugimori
- Department of Preventive Medicine, Daito Bunka University Graduate School of Sports and Health Science, Saitama, Japan
| | - Norio Komatsu
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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20
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Zhang MY, Zhu GQ, Shi KQ, Zheng JN, Cheng Z, Zou ZL, Huang HH, Chen FY, Zheng MH. Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation. Oncotarget 2016; 7:30642-30658. [PMID: 27121321 PMCID: PMC5058707 DOI: 10.18632/oncotarget.8907] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 04/02/2016] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Currently, no consensus exists regarding the optimal oral prophylactic regimens for hepatitis B surface antigen seropositive patients undergoing chemotherapy. We aimed to compare the efficacy of oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of chemotherapy-induced hepatitis B virus (HBV) reactivation and its related morbidity and mortality in patients with chronic HBV (CHB) infection. RESULTS Fifty-two eligible articles consisting of 3892 participants were included. For HBV reactivation, prophylactic treatment with NAs were all significantly superior to no prophylaxis, with odds ratio (OR) from 0.00 (95% confidence interval [CI] 0.00~0.04) for the most effective intervention (tenofovir) to 0.10 (95% CI 0.06~0.14) for the least effective intervention (lamivudine). For secondary outcomes, prophylaxis with NAs also significantly outperformed observation. The results suggested that entecavir reduced the risk of HBV related hepatitis (predicted probability, 83%), HBV related death (68%) and all causes of hepatitis (97%) most efficaciously. It ranked second in decreasing all causes of death (34%). MATERIALS AND METHODS PubMed, Embase and Cochrane Library database were searched for controlled trials up to March 31, 2015. Primary outcome was the incidence of HBV reactivation. Secondary outcomes included the incidence of HBV-related hepatitis and death, all causes of hepatitis and death. Network meta-analysis combined direct and indirect evidence to estimate ORs for the clinical outcomes. A mean ranking and the probability of optimal therapeutic regime was obtained for each treatment based on clinical outcomes. CONCLUSIONS Available evidence suggests that prophylatic therapy with tenofovir and entecavir may be the most potent interventions in prevention of HBV reactivation and HBV-related morbidity and mortality for CHB infection patients undergoing chemotherapy.
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Affiliation(s)
- Min-Yue Zhang
- Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
| | - Gui-Qi Zhu
- Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Ke-Qing Shi
- Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China
| | - Ji-Na Zheng
- Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Zhang Cheng
- Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China
| | - Zhuo-Lin Zou
- Department of Infection Diseases, the First Hospital of Jiaxing, Jiaxing 314000, China
| | - Hong-Hui Huang
- Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
| | - Fang-Yuan Chen
- Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
| | - Ming-Hua Zheng
- Department of Hepatology, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China
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Viganò M, Serra G, Casella G, Grossi G, Lampertico P. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. Expert Opin Biol Ther 2016; 16:917-26. [PMID: 27088278 DOI: 10.1080/14712598.2016.1177017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis. AREAS COVERED This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients. EXPERT OPINION The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient's profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient's clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.
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Affiliation(s)
- Mauro Viganò
- a Hepatology Unit, Ospedale San Giuseppe , Università di Milano , Milan , Italy
| | | | | | - Glenda Grossi
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
| | - Pietro Lampertico
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
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22
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Stansfield LC, Gonsalves WI, Buadi FK. The use of novel agents in multiple myeloma patients with hepatic impairment. Future Oncol 2015; 11:501-10. [PMID: 25675129 DOI: 10.2217/fon.14.270] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate dosing based on metabolism and clearance is important to maintain efficacy while avoiding toxicity. Hepatic impairment (HI) in multiple myeloma patients is rare but well described either due to disease or therapy-related factors. However, limited data are available on the appropriate use and dosing of the novel agent therapeutics in myeloma patients with HI. Furthermore, data on HI secondary to the novel agent toxicity are also sparse. This systematic review highlights the evidence on the use of novel agents like thalidomide, lenalidomide, pomalidomide, bortezomib and carfilzomib in patients with HI as well as their associated hepatic toxicities.
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Lee JY, Lim SH, Lee MY, Kim H, Sinn DH, Gwak GY, Choi MS, Lee JH, Jung CW, Jang JH, Kim WS, Kim SJ, Kim K. Hepatitis B reactivation in multiple myeloma patients with resolved hepatitis B undergoing chemotherapy. Liver Int 2015; 35:2363-9. [PMID: 25832927 DOI: 10.1111/liv.12838] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 03/23/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Despite increasing reports of hepatitis B virus (HBV) reactivation in multiple myeloma (MM), HBV reactivation in patients with resolved hepatitis B [hepatitis B surface antigen (HBsAg)-negative/anti-hepatitis B core antigen antibody (anti-HBc)-positive] is still poorly characterized. The aim of this study was to clarify its frequency and risk factors. METHODS A total of 230 MM patients with resolved hepatitis B were retrospectively reviewed for HBV reactivation and biochemical flare. RESULTS During a median 2.4 years of follow-up, HBV reactivation was diagnosed in 12 patients (5.2%). The cumulative rates of HBV reactivation at 2 years and 5 years were 5% and 8% respectively. A baseline anti-HBs-negative status (P = 0.033) and high-dose therapy/autologous stem-cell transplantation [HDT/ASCT (P = 0.025)] were significant risk factors that were positively associated with HBV reactivation. In subgroup analysis of patients treated with HDT/ASCT (n = 127), a baseline anti-HBs-negative status was the only significant risk factor for HBV reactivation (hazard ratio, 4.64; 95% CI, 1.47-14.7; P = 0.009). DISCUSSION These data show that evaluation of anti-HBc is needed for MM patients, and suggest that monitoring of HBV DNA should be considered for patients with resolved hepatitis B undergoing HDT/ASCT, especially those who are anti-HBs-negative.
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Affiliation(s)
- Ji Yun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Hee Lim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Young Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Haesu Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chul Won Jung
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Ho Jang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Seog Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok Jin Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kihyun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Teh BW, Slavin MA, Harrison SJ, Worth LJ. Prevention of viral infections in patients with multiple myeloma: the role of antiviral prophylaxis and immunization. Expert Rev Anti Infect Ther 2015; 13:1325-36. [PMID: 26489539 DOI: 10.1586/14787210.2015.1083858] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Viral infections are a major cause of morbidity and mortality in patients with myeloma. Over the last decade, treatment of myeloma has undergone a paradigm shift with the use of immunomodulatory drugs, proteasome inhibitors and autologous stem cell transplantation, resulting in changes to risk periods and risk factors for viral infection. Viral infections affecting this patient group fall broadly into reactivation of latent viral infections (e.g., varicella zoster and hepatitis B) and acquisition of acute viral respiratory infections. The periods following autologous stem cell transplantation and progressive disease are identified as increased risk for viral infections. This review focuses on evidence-based prevention strategies for key viral infections, particularly approaches to prophylaxis and immunization. Recommended prevention strategies are summarized using a risk-stratified approach. Further studies evaluating preventative measures for newly identified risk periods are required.
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Affiliation(s)
- Benjamin W Teh
- a 1 Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.,b 2 Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia
| | - Monica A Slavin
- a 1 Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.,c 3 Victorian Infectious Diseases Service, Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
| | - Simon J Harrison
- b 2 Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.,d 4 Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
| | - Leon J Worth
- a 1 Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.,e 5 Department of Medicine, University of Melbourne, Victoria, Australia
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25
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Danhof S, Schreder M, Strifler S, Einsele H, Knop S. Long-term disease control by pomalidomide-/dexamethasone-based therapy in a patient with advanced multiple myeloma: a case report and review of the literature. Case Rep Oncol 2015; 8:189-95. [PMID: 25969681 PMCID: PMC4427147 DOI: 10.1159/000381983] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these ‘novel agents’ remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement. Pomalidomide-based combination therapies are currently under investigation, but data on long-term treatment are lacking. Case Report We present the case of a 68-year-old woman with refractory MM who received pomalidomide in combination with various drugs including anthracyclines, alkylators and proteasome inhibitors. Initially, major hematological toxicities and infectious complications including a hepatitis B virus reactivation were encountered. With careful dose adjustments and selection of combination partners, pomalidomide treatment was maintained for over 4 years and led to a sustained partial remission. In particular, the well-tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with pomalidomide was administered for >30 cycles. Conclusion This case illustrates the value of an individualized approach to myeloma care given an increasing availability of ‘novel agents’. Tailored treatment using these drugs as a backbone is essential to achieve long-lasting responses and minimize side effects.
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Affiliation(s)
- Sophia Danhof
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany
| | - Martin Schreder
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany
| | - Susanne Strifler
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany
| | - Hermann Einsele
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany
| | - Stefan Knop
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Wuerzburg University Medical Center, Wuerzburg, Germany
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26
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Li J, Huang B, Li Y, Zheng D, Zhou Z, Liu J. Hepatitis B virus reactivation in patients with multiple myeloma receiving bortezomib-containing regimens followed by autologous stem cell transplant. Leuk Lymphoma 2015; 56:1710-7. [PMID: 25098429 DOI: 10.3109/10428194.2014.941833] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
To investigate hepatitis B virus (HBV) reactivation and survival in patients with multiple myeloma (MM) receiving bortezomib-containing regimens, we analyzed 139 patients with MM receiving bortezomib-containing regimens in our hospital. Twenty-seven/139 patients were hepatitis B surface antigen positive (HBsAg+) with nine having DNA levels > 500 IU/mL, including four > 1000 IU/mL. All but five HBsAg+ patients were treated with lamivudine or entecavir before chemotherapy until at least 6 months after chemotherapy or autologous stem cell transplant (ASCT). HBV reactivation occurred in six HBsAg+ patients and two HBsAg- patients, including six who received ASCT. Overall survival and progression-free survival of HBsAg- patients were significantly longer than for HBsAg+ patients (both p < 0.01). From these results, we confirmed that the incidence of HBV reactivation was notable in patients with MM receiving bortezomib-containing regimens, especially those who underwent ASCT. HBsAg+ patients with MM had a poorer prognosis than HBsAg- patients. Prophylactic treatment should be prescribed to all patients with HBsAg+ MM for a minimum duration of 12 months.
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Affiliation(s)
- Juan Li
- Department of Hematology, First Affiliated Hospital of Sun Yat-Sen University , Guangdong , P. R. China
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27
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Kim HY, Kim W. Chemotherapy-related reactivation of hepatitis B infection: Updates in 2013. World J Gastroenterol 2014; 20:14581-14588. [PMID: 25356022 PMCID: PMC4209525 DOI: 10.3748/wjg.v20.i40.14581] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/23/2013] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B reactivation is a potentially serious complication of anticancer chemotherapy, which occurs during and after therapy. This condition affects primarily hepatitis B surface antigen (HBsAg)-positive patients, but sometimes HBsAg-negative patients can be at risk, based only on evidence of past infection or occult infection with a low titer of detectable hepatitis B virus (HBV) DNA. The clinical outcomes vary with the different degrees of virologic and biochemical rebound, ranging from asymptomatic elevations in liver enzymes to hepatic failure and even death. Despite the remarkable advancement in the treatment of chronic hepatitis B over the past decade, proper strategies for the prevention and management of HBV reactivation remain elusive. Moreover, with the increasing use of rituximab in patients with lymphoma, HBV reactivation in occult or past infections has become increasingly problematic, especially in HBV-endemic regions. This review addresses the current knowledge on the clinical aspects and management of chemotherapy-related HBV reactivation, updates from recent reports, several unresolved issues and future perspectives.
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28
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Yang JD, Girotra M, Restrepo A, Waheed S, Barlogie B, Duarte-Rojo A. Hepatitis B reactivation in patients with multiple myeloma and isolated positive hepatitis B core antibody: a call for greater cognizance. Ann Hepatol 2014; 13:461-465. [PMID: 24927619 DOI: 10.1016/s1665-2681(19)30855-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
Hepatitis B virus (HBV) reactivation is a well-established complication of severe immunosuppression in patients with hematologic malignancy and positive hepatitis B surface antigen (HBsAg). Patients who receive high-dose chemotherapy, corticosteroids, rituximab, or have a bone marrow transplant are particularly at increased risk for HBV reactivation. However, limited information is available in the literature regarding HBV reactivation in patients with isolated anti-HBc, particularly in the setting of multiple myeloma (MM). We report two cases of HBV reactivation in MM patients with isolated anti-HBc positive with a rather atypical presentation. In conclusion, our cases highlight that clinicians need to be cognizant about this potentially fatal but preventable complication of chemotherapy and immunosuppression.
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Affiliation(s)
- Ju Dong Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
| | - Alejandro Restrepo
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
| | - Sarah Waheed
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
| | - Bart Barlogie
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Department of Medicine, Myeloma Institute for Research and Therapy. University of Arkansas For Medical Science, Little Rock, AR, U.S.A
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29
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Bortezomib induced hepatitis B reactivation. Case Rep Med 2014; 2014:964082. [PMID: 24876846 PMCID: PMC4021848 DOI: 10.1155/2014/964082] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 04/12/2014] [Accepted: 04/13/2014] [Indexed: 11/28/2022] Open
Abstract
Background. It has recently been reported that hepatitis B (HBV) reactivation often occurs after the use of rituximab and stem cell transplantation in patients with lymphoma who are hepatitis B surface antigen (HBsAg) negative. However, clinical data on HBV reactivation in multiple myeloma (MM) is limited to only a few reported cases. Bortezomib and lenalidomide have remarkable activity in MM with manageable toxicity profiles, but reactivation of viral infections may emerge as a problem. We present a case of MM that developed HBV reactivation after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with a history of marginal cell lymphoma was monitored without requiring therapy. In 2009, she developed MM, presenting as a plasmacytoma requiring vertebral decompression and focal radiation. While receiving radiation she developed renal failure and was started on bortezomib and liposomal doxorubicin. After a transient response to 5 cycles, treatment was switched to lenalidomide. Preceding therapy initiation, her serology indicated resolved infection. Serial monitoring for HBV displayed seroconversion one month after change in therapy. Conclusion. Bortezomib associated late HBV reactivation appears to be a unique event that requires further confirmation and brings to discussion whether hepatitis B core positive individuals would benefit from monitoring of HBV activation while on therapy.
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30
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Teh BW, Harrison SJ, Pellegrini M, Thursky KA, Worth LJ, Slavin MA. Changing treatment paradigms for patients with plasma cell myeloma: impact upon immune determinants of infection. Blood Rev 2014; 28:75-86. [PMID: 24582081 DOI: 10.1016/j.blre.2014.01.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 01/22/2014] [Accepted: 01/30/2014] [Indexed: 12/28/2022]
Abstract
Plasma cell myeloma (PCM) is increasing in prevalence in older age groups and infective complications are a leading cause of mortality. Patients with PCM are at increased risk of severe infections, having deficits in many arms of the immune system due to disease and treatment-related factors. Treatment of PCM has evolved over time with significant impacts on immune function resulting in changing rates and pattern of infection. Recently, there has been a paradigm shift in the treatment of PCM with the use of immunomodulatory drugs and proteasome inhibitors becoming the standard of care. These drugs have wide-ranging effects on the immune system but their impact on infection risk and aetiology remain unclear. The aims of this review are to discuss the impact of patient, disease and treatment factors on immune function over time for patients with PCM and to correlate immune deficits with the incidence and aetiology of infections seen clinically in these patients. Preventative measures and the need for clinically relevant tools to enable infective profiling of patients with PCM are discussed.
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Affiliation(s)
- Benjamin W Teh
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Australia
| | - Simon J Harrison
- Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia
| | - Marc Pellegrini
- Walter and Eliza Hall Institute for Medical Research, Parkville, Australia
| | - Karin A Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Australia
| | - Leon J Worth
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Australia
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Australia
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31
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Tan D, Chng WJ, Chou T, Nawarawong W, Hwang SY, Chim CS, Chen W, Durie BGM, Lee JH. Management of multiple myeloma in Asia: resource-stratified guidelines. Lancet Oncol 2013; 14:e571-81. [PMID: 24176575 DOI: 10.1016/s1470-2045(13)70404-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia.
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Affiliation(s)
- Daryl Tan
- Raffles Cancer Center, Raffles Hospital, Singapore, Singapore; Department of Haematology, Singapore General Hospital, Singapore, Singapore.
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32
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Pamukçuoğlu M, Emmez H, Tunçcan OG, Oner AY, Cırak MY, Senol E, Sucak GT. Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections. ACTA ACUST UNITED AC 2013; 19:158-62. [PMID: 23906027 DOI: 10.1179/1607845413y.0000000108] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE AND IMPORTANCE Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6-8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients. CLINICAL PRESENTATION We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients. CONCLUSION Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.
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33
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Goldberg R, Smith E, Bell S, Thompson A, Desmond PV. Bortezomib monotherapy in patients with multiple myeloma is associated with reactivation of hepatitis B. Intern Med J 2013; 43:835-6. [DOI: 10.1111/imj.12180] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2012] [Accepted: 03/10/2013] [Indexed: 11/27/2022]
Affiliation(s)
- R. Goldberg
- St Vincent's Hospital Melbourne; Melbourne; Victoria; Australia
| | - E. Smith
- St Vincent's Hospital Melbourne; Melbourne; Victoria; Australia
| | - S. Bell
- St Vincent's Hospital Melbourne; Melbourne; Victoria; Australia
| | - A. Thompson
- St Vincent's Hospital Melbourne; Melbourne; Victoria; Australia
| | - P. V. Desmond
- St Vincent's Hospital Melbourne; Melbourne; Victoria; Australia
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34
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Hwang JP, Vierling JM, Zelenetz AD, Lackey SC, Loomba R. Hepatitis B virus management to prevent reactivation after chemotherapy: a review. Support Care Cancer 2012; 20:2999-3008. [PMID: 22933131 PMCID: PMC3469760 DOI: 10.1007/s00520-012-1576-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 08/13/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE Reactivation of hepatitis B virus (HBV) infection after chemotherapy can lead to liver failure and death. Conflicting recommendations regarding HBV screening in cancer patients awaiting chemotherapy mean that some patients at risk for HBV reactivation are not being identified and treated with prophylactic antiviral therapy. METHODS We performed a narrative review of the existing evidence regarding screening for and management of HBV infection among patients with cancer using Ovid Medline, PubMed, and the Cochrane Library. RESULTS Our review showed inconsistencies in the definition and management strategies for HBV reactivation. The timeframe of reactivation is variable, and its molecular mechanisms are not clear. There are five effective antiviral agents that can be used as prophylaxis to prevent reactivation of HBV infection in cancer patients; however, the optimal drug and duration of therapy are unknown. Reactivation is more commonly reported in patients with hematologic malignancies receiving rituximab treatment, but reactivation can occur after other chemotherapies and in patients with solid tumors. Screening with all three screening tests-HBsAg, anti-HBc, and anti-HBs-allows the most thorough interpretation of a patient's serologic profile and assessment of reactivation risk; however, decision-making and cost-effectiveness studies are needed to determine optimal screening strategies. CONCLUSIONS Prevention of reactivation of HBV infection depends on identification of patients at risk and initiation of antiviral prophylaxis, but data to guide screening and treatment strategies are lacking. Additional research is necessary to accurately define and predict reactivation, identify best antiviral treatment strategies, and identify cost-effective HBV screening strategies.
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Affiliation(s)
- Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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