CAR+ T-cell lymphoma after cilta-cel therapy for relapsed or refractory myeloma in CARTITUDE-4

The multinational phase 3 CARTITUDE-4 trial evaluated CAR T-cell therapy with ciltacabtagene autoleucel (cilta-cel) for lenalidomide-refractory multiple myeloma after one to three previous lines of therapy. Cilta-cel significantly improved progression-free survival as compared with standard of care. In two CARTITUDE-4 patients receiving cilta-cel, peripheral T-cell lymphoma- not otherwise specified (PTCL-NOS) developed . Monoclonal T cells from both patients had detectable CAR transgene expression and integration. The clinicogenomic features of these CAR transgenic T-cell lymphoproliferative neoplasms suggest that multiple potential intrinsic or extrinsic factors (or both) contributed to their pathogenesis. In the absence of direct evidence, the contribution of insertional mutagenesis to the development of T-cell lymphoma is currently unclear.