Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas

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.