Bispecific Antibody Therapies for Relapsed or Refractory Multiple Myeloma

Bispecific Antibody Therapies for Relapsed/Refractory Myeloma

Bispecific antibodies are offered to nearly all relapsed/refractory patients, with temporary deferral only for patients with active severe infections requiring initial infection control and prophylaxis implementation. Sequencing considerations between BCMA-targeted CAR T-cell therapy and BCMA-directed bispecific antibodies favor CAR-T first, as prior bispecific exposure may reduce subsequent CAR-T efficacy, whereas the reverse sequence appears more favorable.

GPRC5D-targeted bispecifics like talquetamab are being explored as bridging therapy to CAR-T in traditional CAR-T candidate populations (four or more prior lines, triple-class exposed, refractory to immunomodulatory drugs and proteasome inhibitors). However, the treatment landscape is rapidly evolving, with bispecifics moving into earlier lines, including frontline trials for transplant-ineligible patients. This rapid advancement creates uncertainty about optimal sequencing as bispecifics establish earlier roles.

The fundamental question of sequencing after frontline bispecific exposure remains unresolved. If CAR-T should precede bispecifics for the same target in relapsed disease, determining the optimal disease control strategy before CAR-T in patients who received frontline bispecifics presents a challenge. The future role of transplant and optimal treatment sequences five years forward remain uncertain as bispecific antibodies establish their position across multiple lines of therapy.