Blenrep (belantamab mafodotin-blmf)

P2, N=50, Active, not recruiting, PETHEMA Foundation | Completed --> Active, not recruiting

P2, N=50, Completed, PETHEMA Foundation | Not yet recruiting --> Completed

Tyrosine-kinase inhibitor dasatinib rapidly and reversibly inhibited CAR-T activation, serving as an efficient "on/off" switch with the limitation of also inhibiting unmodified T cells...However, conditioning with fludarabine/cyclophosphamide profoundly depletes NK cells, limiting antibody-dependent CAR-T clearance in patients...In this work, we demonstrate that the BCMA-targeting ADC belantamab-mafodotin selectively eliminates BCMA co-expressing CAR-T cells without affecting unmodified T cells. These findings suggest ADCs as a potent, effector cell-independent safety mechanism for CAR-T therapies, potentially enhancing controllability and safety in future clinical applications.

P3, N=325, Active, not recruiting, GlaxoSmithKline | Trial completion date: Jul 2026 --> Mar 2027

P2, N=33, Not yet recruiting, Cristiana Costa Chase, DO | Trial completion date: Oct 2027 --> Jun 2028 | Trial primary completion date: Oct 2025 --> May 2028

P2, N=4, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=20 --> 4

P2, N=62, Recruiting, Mayo Clinic | Trial completion date: May 2027 --> Jun 2034 | Trial primary completion date: May 2026 --> Jun 2029

P1/2, N=153, Recruiting, GlaxoSmithKline | Phase classification: P1 --> P1/2 | N=55 --> 153

P2, N=50, Active, not recruiting, PETHEMA Foundation | Trial completion date: Dec 2025 --> Jun 2026

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.

P2, N=50, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2026 --> Dec 2030 | Trial primary completion date: Dec 2025 --> Dec 2028

P3, N=520, Recruiting, GlaxoSmithKline | Trial completion date: Apr 2032 --> Mar 2031 | Trial primary completion date: Dec 2030 --> Mar 2031