Bispecific T-cell engagers for relapsed/refractory multiple myeloma after solid organ transplantation: A case series.

Abstract

The emergence of bispecific antibodies for multiple myeloma presents a critical unanswered question for solid organ transplant recipients: Can these T-cell dependent therapies overcome concurrent immunosuppression without triggering graft rejection? While teclistamab and similar agents demonstrate remarkable efficacy in immunocompetent patients, their mechanism demands functional T-cells-precisely what calcineurin inhibitors and antimetabolites suppress in transplant recipients. This creates a perilous therapeutic trilemma: (1) Maintaining standard immunosuppression risks blunting bispecific efficacy, (2) reducing immunosuppression may precipitate graft rejection, while (3) both strategies compound already elevated infection risks from dual immunosuppressive effects. Our experience treating two renal transplant recipients with teclistamab reveals these tensions in practice-one patient achieved sustained response without rejection, while another faced infectious complications preceding disease progression. These cases highlight three urgent research priorities: prospective studies to define (a) minimum effective immunosuppression levels during bispecific therapy, (b) biomarkers predicting graft rejection risk, and (c) optimal infection prophylaxis strategies. Until such data exists, clinicians navigate this high-stakes balancing act without evidence, forced to weigh theoretical risks of allograft loss against known mortality from progressive myeloma.