Sequencing Strategies For R/R MM: Choosing Between BCMA- and GPRC5D-Targeting Agents

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Treatment sequencing decisions for bispecific antibodies should prioritize chimeric antigen receptor (CAR) T eligibility assessment as the primary consideration. For CAR T–eligible patients with access to cellular therapy, the choice of bispecific should avoid compromising future CAR T efficacy. However, when CAR T access is uncertain or patients require immediate treatment, initiating bispecific therapy takes precedence, as some treatment is better than delayed optimal treatment.

Currently available BCMA-targeted (teclistamab, elranatamab) and GPRC5D-targeted (talquetamab) bispecific antibodies demonstrate comparable efficacy profiles with impressive overall response rates and depth of response across all agents. The primary differentiating factors lie in their distinct toxicity profiles rather than efficacy differences. BCMA-targeting agents carry increased infection risk, now better managed through prophylactic antivirals and optimized dosing schedules. GPRC5D-targeting agents cause distinctive nail and taste changes that, while not life threatening, can significantly impact quality of life and lead to weight loss in some patients.

Patient-specific factors should guide initial bispecific selection rather than following a predetermined sequence. For malnourished patients, BCMA-targeted therapy may be preferable to avoid taste-related complications. Patients with significant pulmonary disease or high infection risk might benefit from GPRC5D-targeted therapy. When patient factors are neutral, either target class represents a reasonable starting point, with the option to switch targets upon progression, creating a sequential targeting strategy that maximizes treatment options for individual patients.