Treatment Sequencing: Choosing Between CAR T and Bispecifics Across Clinical Scenarios

This segment tackles one of the most nuanced decisions in modern myeloma treatment: determining when to use BCMA CAR T-cell therapy versus a BCMA bispecific antibody. Joseph revisits the earlier case and explains why the patient’s rapid progression made bispecific therapy the preferred initial option. The panel examines factors such as manufacturing delays, difficulty achieving effective bridging therapy, and concerns about T-cell quality in heavily pretreated patients, all of which can complicate CAR T eligibility.

The discussion becomes broader as the panel considers other clinical scenarios. For a slowly progressing, fit patient without extramedullary disease, Joseph would favor CAR T first, citing sequencing data showing superior outcomes when CAR T precedes bispecific therapy. However, in a frail 85-year-old patient, a bispecific would be preferable due to ease of administration and manageable toxicity.

The conversation then shifts to post-CAR-T relapse. Nooka emphasizes that the timing and mechanism of relapse are essential. Loss of BCMA expression—though rare—would make BCMA-directed bispecifics ineffective and require switching targets (e.g., GPRC5D). But for most patients relapsing beyond 12 months, BCMA expression is retained, and bispecifics remain a viable and effective option.

This segment gives clinicians a practical framework for sequencing immune-based therapies, one that considers disease tempo, biology, logistical feasibility, patient fitness, and treatment goals. The experts reinforce that there is no single correct sequence; rather, the decision must be individualized, dynamic, and responsive to real-time clinical conditions.