BCMA-Targeted Therapy Sequencing: Where Will Belantamab Fit in the Current R/R MM Treatment Landscape?

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The discussion focuses on optimal sequencing strategies for BCMA-targeted therapies, particularly belantamab mafodotin (an antibody-drug conjugate) following positive DREAMM-7 and DREAMM-8 trial results. Clinical evidence from the CARTITUDE-2 phase 2 trial demonstrates that prior BCMA-directed therapy significantly impacts subsequent CAR T-cell efficacy, with overall response rates dropping from the 85% to 95% range to approximately 60% in patients with prior BCMA exposure. The duration of prior BCMA therapy and time intervals between treatments emerge as critical factors determining treatment success.

Current treatment paradigm considerations suggest belantamab mafodotin may be most appropriate for patients who are not CAR T-cell candidates, including older or frailer patients who can still benefit from anti-BCMA therapy. However, the sequential use of BCMA-targeted therapies requires careful consideration due to potential cross-resistance mechanisms. The limited real-world data from heavily pretreated patients (median 8 prior lines of therapy) may not fully represent outcomes in earlier-line settings where longer intervals between BCMA therapies might preserve efficacy.

Clinical recommendations emphasize referring eligible patients for CAR T-cell therapy before initiating belantamab mafodotin when possible, based on current evidence suggesting superior outcomes with this sequencing approach. The evolving treatment landscape requires ongoing evaluation of optimal timing and sequencing strategies as more definitive clinical data becomes available, particularly regarding the impact of extended time intervals between BCMA-targeted therapies on subsequent treatment efficacy.