A research center's experience of T-cell redirecting therapies in triple-class refractory multiple myeloma

• CAR-T resulted stronger responses than BiAbs but lacked clinical significance in the case of PFS.

• CAR-T followed by BiAbs could be one of the best treatment sequences for managing triple-class refractory myeloma.

The efficacies of chimeric antigen receptor T (CAR-T) cells and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-T and 37 received BiAbs. CAR-T produced a higher overall response rate (ORR) than BiAbs (97.1% vs. 56.8%, P=0.002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs. 10.8 months; P=0.090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs. 22.6 months; P=0.021). BiAbs following CAR-T yielded a higher ORR and longer PFS2 than did non-redirecting T cell therapies after CAR-T (ORR: 87.5% vs. 50.0%, PFS2: 22.9 vs. 12.4 months). By contrast, BiAbs following BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the non-redirecting T cell therapies (ORR: 28.6%, PFS2: 8.1 months). Even though this is a pooled analysis of different trials with different products and the patient profile is different for CAR-T and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, while the PFS was similar with the two approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.