Optimal Sequencing Strategies for CAR T and Bispecifics in R/R MM
Panelists discuss the critical role of sequencing B-cell maturation antigen (BCMA)-targeted therapies in multiple myeloma, emphasizing that administering chimeric antigen receptor (CAR) T-cell therapy before bispecific antibodies leads to better outcomes, while real-world evidence and emerging guidelines increasingly inform strategic decisions based on treatment timing, disease urgency, and patient-specific factors.
EP: 1.Late-Line R/R: Treatment Landscape
EP: 2.Outcomes and Factors for Consideration When Choosing Between CAR T Therapies
EP: 3.Comparing CAR T Safety, Efficacy in Relapsed/Refractory Multiple Myeloma
EP: 4.Role of Talquetamab as Bridging Therapy for CAR T-Cell Therapy
EP: 5.Optimal Sequencing Strategies for CAR T and Bispecifics in R/R MM
EP: 6.Role of CAR T in Earlier Lines for R/R MM
EP: 7.Non-ICANS and Delayed Neurotoxicity With CAR T: Risk Factors and Ways to Prevent
EP: 8.Real-World Data of SOC Cilta-Cel in R/R MM and Cilta-Cel in Patients With High-Risk Features
EP: 9.Identifying and Treating Patients With Adverse Prognostic Factors
EP: 10.Supportive Care: Infection Disease Prophylaxis and Advice for Community Doctors
EP: 11.Best Practices for Referring Patients for CAR T Therapy
The discussion focused on the sequencing of BCMA-targeted therapies in multiple myeloma, highlighting how prior treatment with BCMA agents—such as bispecific antibodies or antibody-drug conjugates—can impact the efficacy of subsequent CAR T-cell therapy. Clinical trials leading to the approval of these agents excluded patients previously exposed to other BCMA therapies, but real-world data has shown that prior use, particularly within 6 months before CAR T, may reduce CAR T efficacy. Possible mechanisms include BCMA downregulation or loss and T-cell exhaustion, underscoring the importance of strategic sequencing.
Experts emphasized that current evidence supports administering CAR T therapy before bispecifics when possible. Patients who respond to CAR T therapy often retain sensitivity to BCMA-targeted bispecifics upon relapse, with studies showing progression-free survival exceeding 18 months in such scenarios. In contrast, outcomes are generally worse when patients receive bispecific antibodies first, then attempt CAR T. This pattern is further supported by real-world data and emerging consensus guidelines that recommend CAR T first, when access and patient condition allow.
Nonetheless, there are situations where bispecifics may precede CAR T therapy. These include limited access to CAR T, urgent disease progression requiring immediate treatment, or patient preference due to logistical challenges, such as lack of caregiver support. In these cases, bispecifics may be used as “bridging” or “holding” therapy, though ideally not before T-cell collection to avoid compromising CAR T product quality. A recent consensus paper clarified terminology around “holding therapy” (before apheresis) and “bridging therapy” (between apheresis and infusion), recommending bispecifics like talquetamab primarily in the bridging phase. This evolving body of real-world evidence continues to guide clinical decisions in sequencing immunotherapies for optimal outcomes in relapsed/refractory multiple myeloma.
