Abecma (idecabtagene vicleucel)

P2, N=24, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Two patients who had relapsed after CAR T-cell treatment with idecabtagene vicleucel achieved partial and very good partial responses and were successfully transitioned to a second CAR T-cell therapy with ciltacabtagene autoleucel. SVd demonstrates meaningful activity in patients with penta-refractory MM and prior failure of BCMA/GPRC5D-targeted immunotherapies. The ORR of 61%, disease control in 78% of patients, and median PFS of 4.3 months support further evaluation of SVd in this highly refractory setting after failure of BCMA- and GPRC5D-directed approaches.

ORR was 75.4% (95% CI, 63.1-85.2) and CRR was 35.4% (95% CI, 23.9-48.2). The manufacturing success of ide-cel is reliable and consistently high, and when OOS ide-cel products emerged, they demonstrated consistent clinical efficacy and safety.

P2/3, N=312, Recruiting, Celgene | N=214 --> 312

P2, N=32, Recruiting, Massachusetts General Hospital | Trial primary completion date: Dec 2025 --> Aug 2026

P3, N=79, Active, not recruiting, Celgene | N=618 --> 79 | Trial completion date: Aug 2025 --> Nov 2029

P2, N=312, Completed, Celgene | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

MSK AEs represent a common, under-recognized toxicity affecting nearly one-third of BCMA CAR-T recipients, often causing severe and prolonged disability. The identification of predictive baseline PMN-MDSC reduction and persistent inflammatory cytokine elevation provides insights into pathophysiology and suggests potential for risk stratification and targeted therapeutic intervention. These findings warrant prospective validation and development of standardized assessment and management protocols.

P1/2, N=15, Recruiting, Universitaetsklinikum Erlangen AR

P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

In this issue of Cancer Cell, Rade et al. report a longitudinal single-cell atlas of multiple myeloma patients receiving BCMA-directed chimeric antigen receptor (CAR) T cell therapy (ide-cel or cilta-cel) and identifiy features linked to long-term responses, including CD4+ T cell-driven cytotoxicity, memory-biased T cell states, reduced exhaustion, and microenvironment effects.

We then summarize the clinical development and distinguishing features of currently approved BCMA-targeted modalities-CAR T-cell therapies (ide-cel, cilta-cel), bispecific T-cell engagers (teclistamab, elranatamab, linvoseltamab), and the antibody-drug conjugate (belantamab mafodotin)-highlighting their efficacy, toxicity profiles, and practical positioning in relapsed/refractory MM. Finally, we review emerging resistance mechanisms, including γ-secretase-driven sBCMA elevation, ligand-rich APRIL/BAFF niches, and therapy-induced TNFRSF17 lesions, ranging from biallelic deletions to epitope-altering missense mutations and in-frame deletions within the BCMA extracellular domain. These insights inform rational strategies such as γ-secretase inhibition, dual-target CAR T-cells and bispecific T-cell engagers.