BCMA-Directed Therapy Sequencing and Treatment Selection Strategy

Dr. Costa emphasizes that absence of prior BCMA-directed therapy and treatment history represent fundamental elements guiding treatment decisions. The current landscape includes BCMA-directed CAR-T cell therapy, bispecific T-cell engagers, and antibody-drug conjugates. Despite different mechanisms of action, sequential BCMA-directed therapy use carries forward penalties compromising subsequent efficacy.

Sequential BCMA targeting creates cross-resistance patterns where BCMA-directed CAR-T first reduces response rates and shortens disease control with subsequent bispecific therapy, and vice versa. Antibody-drug conjugates similarly affect T-cell engager and CAR-T efficacy when used subsequently. This establishes BCMA as "low-hanging fruit" for this patient, making initial selection critical given that suboptimal first choice compromises future options.

Dr. Costa addresses timing dilemmas with increasing BCMA-directed therapy availability in earlier lines. He strongly advocates against "saving the best for last," citing oncology examples where this proves counterproductive. In multiple myeloma, substantial attrition occurs between treatment lines, with up to 50% of older or frail patients losing fitness or experiencing complications precluding subsequent therapy access.

Clinical experience taught Dr. Costa to avoid strategic delays. When evaluating patients, he focuses on current scenarios, prior exposures, and refractoriness patterns to determine optimal immediate therapy without excessive future sequencing concerns. As bispecific T-cell engagers have produced excellent results in relapsed/refractory multiple myeloma, he advocates immediate implementation rather than compromising with easier approaches while hoping to use superior therapies later, considering this fundamentally self-defeating.