The utilization of immune-checkpoint inhibitors (ICIs) in cancer immunotherapy frequently leads to the occurrence of immune-related adverse events (irAEs), making it generally not recommended for patients with preexisting autoimmune diseases. Hence, we conducted a meta-analysis on safety and efficacy of ICIs in cancer patients with preexisting autoimmune diseases to provide further insights. PubMed, EMBASE, and Cochrane Library were systematically searched until December 20, 2024. The main summary measures used were pooled rate and risk ratio (RR) with 95% confidential interval (CI), which were analyzed using R statistic software. A total of 52 articles were included in the study. When cancer patients with preexisting autoimmune diseases received ICIs treatment, the overall incidence was 0.610 (95% CI: 0.531-0.686) for any grade irAEs, 0.295 (95% CI: 0.248-0.343) for flares, 0.325 (95% CI: 0.258-0.396) for de novo irAEs, 0.238 (95% CI: 0.174-0.309) for grade ≥3 irAEs, and 0.143 (95% CI: 0.109-0.180) for discontinuation due to immunotoxicity. Compared with those without autoimmune diseases, cancer patients with autoimmune diseases experienced a higher risk of any-grade irAEs (RR: 1.23, 95% CI: 1.12-1.35) and discontinuation due to immunotoxicity (1.40, 95% CI: 1.11-1.78). However, no statistically significant differences were observed in the incidence of grade ≥3 irAEs, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between the two groups. During ICIs treatment, irAEs are common among cancer patients with autoimmune diseases, but severe irAEs is relatively low. ICIs are effective in this population, but should be strictly monitored when used to avoid immunotoxicity.

While the association between chronic lymphocytic leukemia (CLL) and a higher incidence of melanoma is well documented, the diagnosis of concurrent high-risk chronic myelomonocytic leukemia (CMML) and metastatic melanoma (MM) has not previously been described. Moreover, the treatment of MM and CMML differ greatly in the mechanism of action of their corresponding antineoplastic therapies: treatment of MM frequently involves immune checkpoint inhibitors (ICI), while patients with CMML receive myelosuppressive agents. Simultaneous management of these malignancies can be nuanced due to the potential impact of one treatment's constituents on the activity of the other and the broad and nonoverlapping array of potential adverse effects of these agents. Here, we describe the clinical course of a patient who was diagnosed with concurrent MM and CMML and our approach to the challenging balance of delivering ICI concurrently with the hypomethylating agent azacitidine and the BCL-2 inhibitor venetoclax.

Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.

Drug-induced liver injury is an important adverse effect and can be caused by various medications, including novel therapeutic agents. The risk stratification of patients susceptible to DILI is a growing field.

The current article highlights new studies on risk stratification regarding risk factors of DILI, prediction of liver injury, and predictors of severe outcomes. Studies on patient demographic and genetic risk factors are discussed, in addition to the potential role of concomitant medications that may affect the risk of DILI.

Although much is known about patient risk factors for DILI, a better combination of these factors into risk scores is needed to predict which patients are particularly susceptible. Knowledge of these risk factors might determine drug treatment in the near future, as well as the need for routine monitoring of liver tests.

To explore the clinical features of pembrolizumab induced psoriasis to provide reference for the optimal treatment of immune checkpoint inhibitor-induced psoriasis. Clinical reports of pembrolizumab induced psoriasis were collected by searching the database until January 31, 2025. The clinical data extracted from the collected articles were retrospectively analyzed. A total of 42 patients were included, 76.2% male, with a median age of 69 years (range 28, 83). These patients included 21 (50.0%) patients with new-onset psoriasis and 21 (50.0%) patients with pre-existing psoriasis. The duration of onset of psoriasis was 8 weeks (range 0.4, 108), and the duration of onset of new psoriasis was longer than that of preexisting psoriasis (9 weeks vs. 7.2 weeks). Plaque psoriasis (38.1%) and psoriatis vulgaris (33.3%) were the most commonly reported phenotypes. After discontinuation or continuation of medication, 90.5% of patients experienced partial or complete improvement of skin symptoms after receiving topical, biologics, and oral systemic treatments. Pembrolizumab induced psoriasis can lead to various types of psoriasis, mainly in elderly and male patients. The pathogenesis and optimal treatment of Pembrolizumab in psoriasis require further investigation.

The development of immune-related adverse events (irAEs) has been associated with improved survival outcomes in non-small cell lung cancer (NSCLC). However, this association's extent across race and ethnicity remains uncertain. We evaluated the association between the development of irAEs and treatment outcomes across racially diverse groups treated at a safety net hospital.

A retrospective chart review was performed to identify patients with advanced NSCLC treated between 2015 and 2020. The incidence of irAEs across racial subgroups was compared using logistic regression analysis. Cox regression analysis was performed to evaluate the association between the development of irAEs and treatment outcomes.

We identified 138 NSCLC patients treated with immune checkpoint inhibitors (ICIs), of whom 50% identified as non-Hispanic Black (NHB). Incidence of irAEs was 28%, with no significant difference between NHB and other racial groups. However, females [OR 2.3, 95% CI, (1.1-4.8)] and patients with Medicaid or MassHealth insurance had a higher incidence of irAEs [OR 2.7 (1.2-5.7)]. Additionally, patients with irAEs had a lower risk of disease progression (multivariable HR 0.46, 95% CI, 0.23-0.92) compared to those without irAEs. The association between irAEs and improved progression free survival (PFS) in NHB patients was similar to the other racial group [median PFS 246 vs 181 days; HR 0.87 (0.58-1.29)].

We demonstrated a similar incidence of irAEs in NHB patients with NSCLC as compared to other racial groups. Patients who developed irAEs experienced significantly improved survival outcomes. This association remained independent of race and ethnicity, underscoring the importance of providing unbiased treatment recommendations.

Patients with inflammatory arthritis treated with immune checkpoint inhibitors (ICIs) for melanoma face unique challenges, including disease flares and reduced treatment efficacy. Evidence on the survival impact of pre-existing arthritis in this population remains limited.

We conducted an observational cohort study using data from two Danish national registries, DANBIO and DAMMED, including patients with melanoma and pre-existing inflammatory arthritis treated with ICIs. Cases were matched with controls without arthritis based on sex, age, melanoma subtype, disease stage, and treatment regimen. Outcomes included overall survival (OS), progression-free survival (PFS)/recurrence-free survival (RFS), changes in rheumatic disease activity, and healthcare utilization.

Seventy-five patients with inflammatory arthritis were identified, initiating 91 ICI treatment courses. Patients with arthritis demonstrated poorer OS (HR 1.4, 95 % CI: 1.04-1.91) and PFS/RFS (HR 1.5, 95 % CI: 1.13-1.94) compared to controls. Subgroup analysis of immunosuppressed patients yielded similar results. Rheumatic disease activity increased post-ICI initiation (mean DAS28 Δ +0.48, p = 0.001), while rheumatologic healthcare utilization decreased.

Patients with inflammatory arthritis have poorer OS and PFS/RFS following ICI therapy for melanoma, partly attributable to baseline immunosuppressive treatment. These findings underscore the need for enhanced multidisciplinary management to optimize outcomes and address the survival gap in this population.

Immune checkpoint molecules like PD-1 and its ligand PD-L1 and CTLA-4 are important regulators of the immune system. Medications blocking these pathways, immune checkpoint inhibitors, have been used to treat a variety of malignancies, while drugs agonizing these pathways, like abatacept, have been used in treating autoimmune diseases. Modulation of the PD-1/PD-L1 axis has become important for rheumatologists to understand in several different clinical scenarios. Currently, PD-1 agonists are being developed for treatment of rheumatoid arthritis (RA). In addition to patients with RA being potentially treated with PD-1 agonists, patients with rheumatoid arthritis may be treated with anti-PD-1/PD-L1 immune checkpoint inhibitors if they develop cancer. Finally, patients treated with immune checkpoint inhibitors may develop de novo inflammatory arthritis and be referred to rheumatology for management. In all three scenarios, there remain many unanswered clinical and translational questions. The parallel development of therapeutics antagonizing and agonizing the PD-1/PD-L1 pathway presents a unique chance for discovery in inflammatory arthritis.

Immune checkpoint inhibitors (ICIs) improve overall survival (OS) and progression-free survival (PFS) in many types of malignancies but can result in off-target immune-related adverse events including inflammatory arthritis (ICI-associated inflammatory arthritis [ICI-IA]), which can persist even after ICI cessation. We aimed to examine the proportion of patients with ICI-IA who develop chronic ICI-IA and describe characteristics and outcomes associated with chronic ICI-IA.

We identified patients from the Canadian Research Group of Rheumatology in Immuno-Oncology retrospective cohort who developed de novo ICI-IA with at least three months of follow-up after ICI cessation. Chronic ICI-IA was defined as symptoms or ongoing immunosuppression lasting beyond three months after ICI discontinuation. Acute ICI-IA was defined as resolution of ICI-IA symptoms and discontinuation of immunosuppression within three months of ICI discontinuation. OS and PFS were assessed with Kaplan-Meier curves. Landmark multivariable Cox proportional hazard models for OS and PFS were conducted.

The study cohort included 119 patients. A total of 15 patients (13%) had acute ICI-IA, whereas 104 (87%) had chronic ICI-IA. Patients with chronic ICI-IA were more likely to be White and to have polyarthritis at presentation. After adjusting for age, sex, tumor type, stage of cancer, ICI-IA treatment, and time from ICI initiation to ICI-IA onset, patients with chronic ICI-IA had greater PFS from ICI initiation (adjusted hazard ratio 0.27, 95% confidence interval 0.08-0.98; P = 0.046). Adjusted hazard ratio for OS was similar between those with acute versus chronic ICI-IA.

ICI-IA frequently persists after ICI discontinuation. Chronic ICI-IA is associated with improved PFS, but not OS, as compared to acute ICI-IA.

Immunotherapy has changed the treatment landscape for patients with cancer in the past decade. Immune checkpoint inhibitor (ICI)-based therapies have proven effective in a range of malignancies, including liver and gastrointestinal cancers, but they can cause diverse off-target organ toxicities. With the increasingly wider application of these drugs, immune-mediated liver injury from ICIs has become a commonly encountered challenge in clinical hepatology and gastroenterology. In this Review, we discuss the evidence from human and animal studies on the immunological mechanisms of immune-mediated liver injury from ICIs and summarize its clinical features and practical considerations for its management.

Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use. Multivariate Cox proportional hazard models and Kaplan Meier method were used to assess risk of developing ACs among the groups. Subgroup analysis was done to evaluate risk of ACs in patients receiving cytotoxic T-lymphocyte-associated protein 4 inhibitor (CTLA4i) versus program cell death protein 1 inhibitor (PD1i) and program death ligand 1 inhibitor (PDL1i) inhibitors and combination treatment (CT) (CTLA4 + PD1i/PDL1i) versus PD1i/PDL1i.

Patients who received ICIs (2.03% of total population) were younger (68.7 ± 12.6 vs 71.8 ± 13.9; P < 0.001), predominantly male (54% vs 41%; P < 0.0001), and White (68% vs 58%; P < 0.0001), had lower odds of developing systemic lupus erythematosus (SLE) (0.366% vs 0.437%, odds ratio [OR] 0.837; P = 0.0005) and systemic sclerosis (0.108% vs 0.135%, OR 0.796; P = 0.0151), and had higher odds of developing rheumatoid arthritis (RA) (2.194% vs 1.752%, OR 1.258; P < 0.0001 with hazard ratio 1.746; P < 0.0001). There was no significant difference in developing vasculitis, dermatopolymyositis, and psoriatic arthritis when compared to patients who did not receive ICIs. The prevalence of ACs remained true after propensity score matching, except that there was no difference compared with the prevalence of SLE (0.37% [n = 391] vs 0.393% n = 415], OR 0.942 [0.82-1.082]; P = 0.3970).

Patients receiving ICIs have an increased risk of developing ACs, especially RA. There needs to be a high index of suspicion and awareness about ACs for prescribers of ICIs.

A 74-year-old woman's persistent hyponatraemia led to the discovery of an adenosquamous carcinoma within an intrapulmonary bronchogenic cyst (IPBC), diagnosed 59 years prior. This is the first reported case of such a transformation in an IPBC. An adenosquamous carcinoma, originating from an intrapulmonary bronchogenic cyst identified 59 years prior, was discovered during the workup for a patient's unexplained, persistent hyponatraemia.

The presence of pre-existing autoimmune disease (PAD) with metastatic non-small cell lung cancer (mNSCLC) poses challenges in the use of immune checkpoint inhibitors (ICI). This study investigated factors influencing ICI utilization in older adults with mNSCLC and PAD.

A retrospective cohort study with a 12-month baseline prior to treatment initiation was conducted using the SEER-Medicare data. Patients aged 66 years and above diagnosed with mNSCLC between January 2015 and December 2017, who initiated immunotherapy only/chemoimmunotherapy (IT/CIT) or chemotherapy only (CIT) and had at least one PAD diagnosed any time before treatment initiation, were included. Multiple factors, guided by the Model of Health Services Utilization, were analyzed using multivariable logistic regression. Adjusted odds ratios (aORs) and 95.0% CIs were reported.

Among 1,319 patients initiating first-line (1L) systemic therapy, 22.3% received IT/CIT and 77.7% received CT. Patients initiating IT/CIT were more likely to be 76-80 years old (aOR = 1.70, 95.0% CI = 1.02-2.81) and > 80 years old (aOR = 2.49, 95.0% CI = 1.46-4.25), reside in South (aOR = 2.32, 95.0% CI = 1.36-3.96) and West (aOR = 2.27, 95.0% CI = 1.44-3.60) SEER regions, diagnosed in 2016 (aOR = 6.36, 95.0% CI = 3.06-13.22) and 2017 (aOR = 40.45, 95.0% CI = 19.70-83.07), having a longer time to treatment initiation (aOR = 1.14, 95.0% CI = 1.08-1.19), having non-squamous tumor histology (aOR = 1.511, 95.0% CI = 1.048-2.179), and having a prior hospitalization (aOR = 1.63, 95.0% CI = 1.14-2.33). These patients were less likely to have recently used an immunosuppressant (IS) (aOR = 0.06, 95.0% CI = 0.04-0.10).

Several factors, such as age, region, cancer diagnosis year, time to treatment initiation, and recent IS use, intricately shape treatment decisions. Further in-depth research on each of these factors is imperative to optimize strategies for this distinctive patient population.

Patients with cancer and an underlying autoimmune disease who are considering immune checkpoint blockers (ICBs) need to know about the benefits and risks of severe immune-related adverse events and flares of the autoimmune condition.

This study aims to develop and alpha test an educational website for patients with cancer.

Learning topics, images, and website architecture (including flow and requirements) were developed and iteratively reviewed by members of a community scientist program, a patient advisory group, and content experts. Alpha testing was performed, measuring the site's usability using the Suitability Assessment of Materials and its acceptability using the Ottawa Acceptability Measure.

The website included a home page; general information about ICBs; comprehensive modules on the benefits and risks of ICBs for patients with cancer and preexisting autoimmune diseases; general wellness information; and features such as a quiz, additional resources, and a glossary. For the alpha testing, 9 users assessed the newly developed website. Patient reviewers (n=5) had rheumatoid arthritis, Crohn disease, Sjogren syndrome, or vasculitis. Health care provider reviewers (n=4) were medical oncologists or rheumatologists. The median Suitability Assessment of Materials rating was 75 (IQR 70-79; range 0-100) for patients versus 66 (IQR 57-72; range 0-100) for providers (scores ≥70 indicate no substantial changes needed). Recommendations for improvement, mostly involving navigation and accessibility, were addressed. All participants expressed that the website was acceptable and balanced in terms of discussion of benefits and harms. Because half (2/4, 50%) of the providers suggested we increase the amount of information, we extended the content on the impact of having an autoimmune disease when considering ICB treatment, the probability of flares, and the management of flares in this context.

The feedback led to minor revisions to enhance readability, navigation, and accessibility, ensuring the website's suitability as a decision-making aid. The newly developed website could become a supporting tool to facilitate patient-physician discussion regarding ICBs.

Tumor immunotherapy has emerged as a promising approach in cancer treatment in recent years, offering vast potential. This method primarily involves targeting and inhibiting the suppressive checkpoints present in different immune cells to enhance their activation, ultimately leading to tumor regression. However, tumor cells exploit the surrounding immune cells and tissues to establish a tumor microenvironment (TME) that supports their survival and growth. Within the TME, the efficacy of effector immune cells is compromised, as tumor cells exploit inhibitory immune cells to suppress their function. Furthermore, certain immune cells can be co-opted by tumor cells to facilitate tumor growth. While significantly enhancing the body's tumor immunity can lead to tumor regression, it can also result in severe toxic side effects and an inflammatory factor storm. As a consequence, patients often discontinue treatment due to immune-related adverse events (irAEs) or, in extreme cases, succumb to toxic side effects before experiencing tumor regression. In this analysis, we examined several remission regimens for irAEs, each with its own drawbacks, including toxic side effects or suppression of tumor immunotherapy, which is undesirable. A recent research study, specifically aimed at downregulating intestinal epithelial barrier permeability, has shown promising results in reducing the severity of inflammatory bowel disease (IBD) while preserving immune function. This approach effectively reduces the severity of IBD without compromising the levels of TNF-α and IFN-γ, which are crucial for maintaining the efficacy of tumor immunotherapy. Based on the substantial similarities between IBD and ICI colitis (combo immune checkpoint inhibitors-induced colitis), this review proposes that targeting epithelial cells represents a crucial research direction for mitigating irAEs in the future.

Background and Objectives: Immune checkpoint inhibitors (ICIs), which target immune checkpoints in cancer cells, are increasingly used as a mainstay in anticancer treatment. The combination of atezolizumab and bevacizumab is also a first-line treatment for hepatocellular carcinoma (HCC). However, ICIs can cause immune-related adverse events (IrAEs) which range from mild to severe, potentially leading to the need for discontinuing immunotherapy. We report a case of a pneumothorax, a rare side effect caused by IrAEs. Materials and Methods: This paper reports a case of a 78-year-old male HCC patient who developed a recurrent pneumothorax, suspected to be an adverse effect of ICIs. Results: The patient was a current smoker with a 30 pack-year smoking history. Prior to initiating ICIs, a chest CT scan showed mild emphysema and fibrosis attributable to smoking. Following ICI treatment, the patient developed a recurrent pneumothorax. Further tests revealed no underlying cause for the pneumothorax other than the ICIs and smoking, and there were no signs of intrapulmonary metastasis or pneumonitis. Conclusions: When a pneumothorax occurs in a patient undergoing immunotherapy, it is important to consider it as a potential adverse effect of the treatment. Special attention should be given to the possibility that immunotherapy may exacerbate underlying lung conditions. Patients should be advised on the importance of smoking cessation. As there are currently no guidelines for resuming immunotherapy after a pneumothorax, it is crucial to weigh the risks and benefits and consider dose reduction or discontinuation of the medication.

Immune checkpoint inhibitor (ICI) therapy, which targets programmed cell death protein 1, has demonstrated enhanced survival outcomes in numerous patients with cancer. Historically, individuals with autoimmune diseases have been excluded from clinical trials involving cancer immunotherapies due to concerns about the potential worsening of their underlying autoimmune conditions. In the present case report, a patient with non-small cell lung cancer and bullous pemphigoid (BP) who underwent treatment with the ICI pembrolizumab is described. In this specific clinical case, no severe exacerbation of the underlying autoimmune disease was observed. Contrarily, the patient not only tolerated pembrolizumab well but also experienced amelioration of the BP lesions after the treatment. This case challenges the conventional exclusion criteria for ICI therapy in patients with autoimmune diseases, suggesting the potential safety and efficacy of such treatments in this specific population. However, further investigations and larger-scale studies are warranted to validate these findings and provide a more comprehensive understanding of the implications of ICI therapy in patients with autoimmune comorbidities.

This case report discusses a patient with systemic lupus erythematosus (SLE) treated with low-dose azathioprine who developed progressive multifocal leukoencephalopathy (PML). PML is a rare, severe, demyelinating disease linked to John Cunningham polyomavirus (JCV) reactivation.Treated with pembrolizumab, an immune checkpoint inhibitor, the patient initially improved. However, after the fourth dose, her condition rapidly worsened resulting in treatment discontinuation and death. Similar cases highlight the complex interplay of factors in PML development in SLE patients, including immunosuppression and genetic factors. The use of pembrolizumab in PML and SLE necessitates careful consideration of potential complications.

Evidence from multiple observational studies suggests that ankylosing spondylitis (AS) is associated with leukemia and lymphocytic malignancies. However, the obtained results are inconsistent, and the causal relationship still needs to be determined. In this context, we utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between AS and leukemia and lymphocytic malignancies.

The analysis was conducted through published genome-wide association studies (GWAS). We obtained genetic data on AS as the exposure and leukemia, including lymphocytic leukemia, myeloid leukemia, and lymphocytic malignancies including lymphoma, multiple myeloma (MM) as the endpoint. The main method to evaluate causality in this analysis was the inverse variance weighting (IVW) technique. Additionally, we employed the weighted mode, weighted median, and MR-Egger regression for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multi-effect analyses are carried out.

In a random-effects IVW analysis, we found that genetic susceptibility to AS was associated with an increased risk of leukemia (OR = 1.002; 95%CI, 1.001-1.003; p = 0.003) and an increased risk of lymphocytic leukemia [OR = 1.001; 95% CI, (1.000-1.002), p = 0.008]. There was no evidence that AS was associated with lymphoma, myeloid leukemia, and MM.

Our research indicates that AS was associated with an elevated risk of leukemia, and further analysis of specific types of leukemia showed that the risk of lymphocytic leukemia was associated with AS. Our findings highlight the importance of active intervention and monitoring to mitigate leukemia, especially lymphocytic leukemia risk in patients with AS.

Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs.

We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths.

A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease.

Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.

Nivolumab has been approved for treating ≥ 10 cancer types. However, there is limited information on the incidence of rare, but potentially serious, treatment-related adverse events (TRAEs), as well as notable TRAEs in patients with certain medical disorders or older patients in Japan.

We performed pooled analyses of data from published post-marketing surveillance in Japan of nivolumab monotherapy for patients with malignant melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and gastric cancer to determine the frequencies of 20 categories of TRAEs of special interest overall and in patient groups with higher perceived safety risks (history of autoimmune disease, interstitial lung disease, tuberculosis, or hepatitis B/C; patients vaccinated during nivolumab treatment; and older patients [≥ 75 years]).

The overall population comprised 7421 patients treated with nivolumab. TRAEs were reported in 49.1% of patients, with grade ≥ 3 TRAEs in 16.7%. Endocrine disorders (14.4%), hepatobiliary disorders (10.9%), and interstitial lung disease (7.0%) were the three most common categories (any grade). The incidences of rare TRAEs with high risk of becoming serious, which occurred in < 1% of patients, were consistent with those in previous reports. The frequencies of TRAEs were not markedly increased in the specified patient groups relative to the overall population.

To our knowledge, this is the largest study examining the safety of nivolumab-treated patients in real-world clinical practice including rare but potentially serious TRAEs. We found no new signals in the safety of nivolumab among the patient groups relative to the overall population, and no additional safety measures are required in these groups. Trial registration UMIN000048892 (overall analysis), JapicCTI-163272 (melanoma), Japic-163271 (non-small cell lung cancer), JapicCTI-184071 (head and neck cancer), JapicCTI-184070 (gastric cancer), and JapicCTI-184069 (renal cell cancer).

Immune checkpoint inhibitors (ICIs) are effective antitumor agents but are associated with immune-related adverse events. ICI-induced psoriasis commonly presents in patients with a history of psoriasis but may occur de novo, and it has a significant physical and psychosocial impact. ICI-induced and non-ICI-induced psoriasis are likely mediated by similar cytokines, and similar treatments are employed. Topical treatment often suffices, and when needed, several systemic treatments appear to be effective without impacting antitumor response. Development of psoriasis may indicate a superior response to ICIs. Thus, recognition and management of ICI-induced psoriasis is essential to avoid ICI interruption and maximize therapeutic potential.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC).

The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR.

In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models.

We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs). Rh-irAEs mimic primary rheumatic diseases including arthritis, polymyalgia rheumatica, myositis, vasculitis, sarcoidosis, and sicca. This article summarizes the latest evidence regarding the utility of laboratory investigations in Rh-irAEs.

Immune checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancer types. Patients with preexisting autoimmune diseases may be vulnerable to underlying disease flare as well as immune-related adverse events from ICIs. There has also been concern that immunosuppression needed to control the autoimmune disease may blunt ICI efficacy. Much of the literature is focused on diverse preexisting autoimmune diseases, which may limit conclusions to specific diseases. There is a growing literature of specific diseases, such as preexisting rheumatoid arthritis, investigating outcomes after ICI.

The development of sicca in patients treated with immune checkpoint inhibitors (ICIs) is undoubtedly an underestimated complication, but one whose functional consequences and impact on quality of life are significant for patients. This update aims to review the frequency of this complication and different clinical pictures. The authors also propose a diagnostic and therapeutic approach to guide clinicians in daily practice.

This review focuses on special populations poorly represented in current evidence-based practice for metastatic renal cell carcinoma (mRCC). This includes the elderly and frail, patients on immunosuppression or with autoimmune diseases, patients with brain, liver, and/or bone metastases, and RCC with sarcomatoid features.

Certain populations are poorly represented in current trials for mRCC. Patients with central nervous system (CNS) metastases are often excluded from first-line therapy trials. Modern doublet systemic therapy appears to benefit patients with bone or liver metastases, but data supporting this conclusion is not robust. Post-hoc analyses on patients with sarcomatoid differentiation have shown improved response to modern doublet therapy over historical treatments. The elderly are underrepresented in current clinical trials, and most trials exclude all but high-performing (nonfrail) patients, though true frailty is likely poorly captured using the current widely adopted indices. It is difficult to make conclusions about the efficacy of modern therapy in these populations from subgroup analyses. Data from trials on other malignancies in patients with autoimmune diseases or solid organ transplant recipients on immunosuppression suggest that immune checkpoint inhibitors (ICIs) may still have benefit, though at the risk of disease flare or organ rejection. The efficacy of ICIs has not been demonstrated specifically for RCC in this group of patients.

The elderly, frail, and immunosuppressed, those with tumors having aggressive histologic features, and patients with brain, bone, and/or liver metastases represent the populations least understood in the modern era of RCC treatment.

Patients with rheumatologic preexisting autoimmune disease (PAD) have not been enrolled in clinical trials of immune checkpoint inhibitors (ICIs). Therefore, the risks and benefits of ICI therapy in such patients are unclear. Herein, we investigated the safety and efficacy of ICIs in rheumatologic PAD patients through a meta-analysis.

The PubMed, Cochrane Library, Embase and Web of Science databases were searched for additional studies. We analyzed the following data through Stata software: incidence of total irAEs (TirAEs), rate of flares, incidence of new on-set irAEs, rate of discontinuation, objective response rate (ORR) and disease control rate (DCR).

We identified 23 articles including 643 patients with rheumatologic PAD. The pooled incidences of TirAEs, flares and new-onset irAEs were 64% (95% CI 55%-72%), 41% (95% CI 31%-50%), and 33% (95% CI 28%-38%), respectively. In terms of severity, the incidences were 7% (95% CI 2%-14%) for Grade 3-4 flares and 12% (95% CI 9%-15%) for Grade 3-4 new-onset irAEs. Patients with RA had a greater risk of flares than patients with other rheumatologic PADs did (RR = 1.35, 95% CI 1.03-1.77). The ORR and DCR were 30% and 44%, respectively. Baseline anti-rheumatic treatment was not significantly associated with the frequency of flares (RR = 1.05, 95% CI 0.63-1.77) or the ORR (RR = 0.45, 95% CI 0.12-1.69).

Patients with rheumatologic PAD, particularly those with RA, are susceptible to relapse of their rheumatologic disease following ICI therapy. ICIs are also effective for treating rheumatologic PAD patients. PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): number CRD 42,023,439,702.

The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness.

Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results.

Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR).

Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%).

This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

Clinically amyopathic dermatomyositis (CADM) with a positive anti-MDA5 antibody titer is often associated with lethal rapidly progressive interstitial lung disease (RP-ILD). Despite the widespread use of immune checkpoint inhibitors (ICIs) in practice, there is no report of CADM with positive anti-MDA5 antibodies as their immune-related complication. We present a case of malignant mesothelioma who developed RP-ILD accompanied by distinct skin manifestations following the administration of nivolumab. Postmortem assessment of stored samples revealed a pre-existing positive titer of anti-MDA5 antibody, further augmented following ICI use, suggesting the possible value of serum screening for better risk stratification of this lethal complication.

This review outlines the most up-to-date metastatic melanoma treatment recommendations and relevant risks for patients with solid organ transplants, patients with renal dysfunction, and patients with preexisting autoimmune conditions. These specific treatment populations were excluded from the original clinical trials, which studied immune checkpoint inhibitors and BRAF/MEK inhibitors in the advanced melanoma setting. We have synthesized the current body of literature, mainly case series and retrospective analyses, to reflect the evidence for the treatment of these special patient populations at present.

Traditional chemotherapy has been ineffective in the treatment of metastatic melanoma. Until the use of checkpoint inhibitors, patients had very limited survival. Since the original US Food and Drug Administration approval of ipilimumab over a decade ago, the armamentarium of immunotherapeutic agents has expanded to include programmed cell death protein 1 and lymphocyte activation gene 3 antibodies, requiring a nuanced approach to the selection of frontline treatments, managing patients through recurrence and progression, and determining length of therapy. Herein, we review the existing evidence supporting current standard immunotherapy regimens and discuss the clinical decision-making involved in treating patients with metastatic melanoma with checkpoint inhibitors.

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.

To evaluate the frequency and severity of irAEs in patients with pre-existing autoimmunity, including irAE-related morbidity and mortality, irAE-related management and resolution, and outcome of ICI rechallenge, to better understand the treatment options for this vulnerable patient population.

We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests.

Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, p = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls).

Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.

Immune checkpoint inhibitors (ICIs) are the standard of care for a growing number of malignancies. Unfortunately, they are associated with a broad range of unique toxicities that mimic the presentations of primary autoimmune conditions. These adverse events are termed immune-related adverse events (irAEs), of which ICI-lupus erythematosus (ICI-LE) constitutes a small percentage. Our review aims to describe the available literature on ICI-LE and ICI treatment for patients with pre-existing lupus. Most diagnoses of ICI-LE had findings of only cutaneous lupus; four diagnoses of ICI-LE had systemic lupus manifestations. Over 90% (27 of 29) of cases received anti-PD-1/PDL-1 monotherapy, 1 received combination therapy, and 1 received only anti-CTLA-4 treatment. About three-fourths (22 of 29 or 76%) of patients with ICI-lupus were managed with topical steroids, 13 (45%) received hydroxychloroquine, and 10 (34%) required oral corticosteroids. In our case series, none of the patients with pre-existing lupus receiving ICI therapy for cancer had a flare of their lupus, but few had de novo irAE manifestations, all of which were characterized as low-grade. The review of the literature yielded seven ICI-LE flares from a total of 27 patients with pre-existing lupus who received ICI. Most flares were manageable without need for ICI cessation.

Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system. These cardiac irAEs include conditions like myocarditis, atherosclerosis, pericarditis, arrhythmias, and cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). This review delves into the mechanisms of approved ICIs (CTLA-4, PD-1, PD-L1, and LAG-3) and upcoming options like Tim-3 and TIGIT. It explores the use of ICIs in cancer treatment, supported by both preclinical and clinical data. Additionally, it examines the mechanisms behind cardiac toxic irAEs, focusing on ICI-associated myocarditis and atherosclerosis. These insights are vital as ICIs continue to revolutionize cancer therapy, offering hope to patients, while also necessitating careful monitoring and management of potential side effects, including emerging cardiac complications.

Immune-related adverse events (irAEs) are toxicities that arise after the administration of monoclonal antibodies targeting immune checkpoints (immune checkpoint inhibitors [ICIs]) in patients with cancer. They can occur at any time after initiation of ICI treatment, with a broad clinical phenotype that can be organ-specific or systemic. Although most irAEs manifest as mild to moderate signs and symptoms, severe forms of irAEs can lead to irreversible organ failure and have acute life-threatening presentations. Treatment should be tailored to the specific organ involved and the severity. Glucocorticoids are the first-line treatment for most irAEs, with immunosuppressants and biologics mainly used as second-line treatments.

To investigate immunomodulator use, risk factors and management for rheumatoid arthritis (RA) flares, and mortality for patients with pre-existing RA initiating immune checkpoint inhibitors (ICI) for cancer.

We performed a retrospective cohort study of all patients with RA meeting 2010 ACR/EULAR criteria that initiated ICI for cancer at Mass General Brigham or Dana-Farber Cancer Institute in Boston, MA (2011-2022). We described immunomodulator use and changes at baseline of ICI initiation. We identified RA flares after baseline, categorized the severity, and described the management. Baseline factors were examined for RA flare risk using Fine and Gray competing risk models. We performed a landmark analysis to limit the potential for immortal time bias, where the analysis started 3 months after ICI initiation. Among those who survived at least 3 months, we examined whether RA flare within 3 months after ICI initiation was associated with mortality using Cox regression.

Among 11,901 patients who initiated ICI for cancer treatment, we analyzed 100 pre-existing RA patients (mean age 70.3 years, 63 % female, 89 % on PD-1 monotherapy, 50 % lung cancer). At ICI initiation, 71 % were seropositive, 82 % had remission/low RA disease activity, 24 % were on glucocorticoids, 35 % were on conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and 10 % were on biologic or targeted synthetic DMARDs. None discontinued glucocorticoids and 3/35 (9 %) discontinued DMARDs in anticipation of starting ICI. RA flares occurred in 46 % (incidence rate 1.84 per 1000 person-months, 95 % CI 1.30, 2.37); 31/100 flared within 3 months of baseline. RA flares were grade 1 in 16/46 (35 %), grade 2 in 25/46 (54 %), and grade 3 in 5/46 (11 %); 2/46 (4 %) required hospitalization for RA flare. Concomitant immune-related adverse events occurred in 15/46 (33 %) that flared. A total of 72/100 died during follow-up; 21 died within 3 months of baseline. Seropositivity had an age-adjusted sdHR of 1.95 (95 % CI 1.02, 3.71) for RA flare compared to seronegativity, accounting for competing risk of death. Otherwise, no baseline factors were associated with RA flare, including cancer type, disease activity, RA duration, and deformities. 9/46 (20 %) patients had their ICI discontinued/paused due to RA flares. In the landmark analysis among 79 patients who survived at least 3 months, RA flare in the first 3 months was not associated with lower mortality (adjusted HR 1.24, 95 % CI 0.71, 2.16) compared to no RA flare.

Among patients with pre-existing RA, few changed immunomodulator medications in anticipation of starting ICI, but RA flares occurred in nearly half. RA flares were mostly mild and treated with typical therapies. Seropositivity was associated with RA flare risk. A minority had severe RA flares requiring disruption of ICI, and RA flares were not associated with mortality.