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World J Clin Oncol. Oct 24, 2021; 12(10): 882-896
Published online Oct 24, 2021. doi: 10.5306/wjco.v12.i10.882
Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas
Emanuele Cencini, Alberto Fabbri, Bianca Mecacci, Monica Bocchia
Emanuele Cencini, Alberto Fabbri, Bianca Mecacci, Monica Bocchia, Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena 53100, Italy
Author contributions: Cencini E prepared the first draft of the manuscript; Fabbri A and Mecacci B contributed to reviewing and revising the manuscript; Cencini E and Bocchia M coordinated the preparation of the manuscript.
Conflict-of-interest statement: The authors declare having no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Emanuele Cencini, MD, PhD, Doctor, Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Policlinico Le Scotte, viale Bracci 16, Siena 53100, Italy. emanuele.cencini@ao-siena.toscana.it
Received: March 3, 2021
Peer-review started: March 3, 2021
First decision: July 6, 2021
Revised: July 7, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 24, 2021
Processing time: 199 Days and 20.7 Hours
Abstract

T-cell lymphomas (TCLs) represent a group of lymphoid neoplasms characterized by an aggressive clinical course, even after an anthracycline-containing regimen. Novel agents for patients with relapsed/refractory TCL are urgently needed. Lenalidomide is an oral drug with immunomodulatory, antiangiogenic and direct antineoplastic effects. These peculiar mechanisms of action make TCL an attractive target for lenalidomide. We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL, including cutaneous TCL (CTCL) and adult T-cell lymphoma/leukemia (ATLL). In the ATLL-002 study, the overall response rate (ORR) was 42% and median progression-free survival (PFS) and overall survival were 3.8 mo and 20.3 mo, respectively. In a phase II trial for CTCL, ORR was 28% and median PFS and overall survival were 8 mo and 43 mo, respectively. For nodal peripheral TCL, ORR was between 10% and 43% in three clinical trials, with a median PFS of about 4 mo, even if some patients had a durable response. Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible. Combination strategies did not improve PFS. In conclusion, lenalidomide could represent a suitable treatment option for relapsed/refractory TCL, especially for neoplasms with a T-follicular helper origin, such as angioimmunoblastic TCL.

Keywords: T-cell lymphomas; Lenalidomide; Therapy; Survival; Safety; T follicular helper

Core Tip: T cell lymphoma (TCL) are rare. Lenalidomide is an oral drug with an immunomodulatory, antiangiogenic and direct antineoplastic effect. These peculiar mechanisms of action makes TCL an attractive target for lenalidomide. We have identified 5 clinical trials in which lenalidomide monotherapy was investigated to treat TCL, including cutaneous TCL and adult T-cell lymphoma/leukemia. Overall response rate was between 10 % and 43%, with prolonged response in a significant proportion of cases and manageable toxicity. Lenalidomide could represent a suitable treatment option for R/R TCL, especially for neoplasms with a T-follicular helper origin, such as angioimmunoblastic TCL.