Multiple myeloma therapy has been reshaped by anti-CD38 antibodies, BCMA-directed cell therapy, and bispecific antibodies, extending both the depth and duration of response across the disease course.
Newly diagnosed disease
The trend is toward antibody-containing quadruplet regimens. Adding the anti-CD38 antibody isatuximab to bortezomib, lenalidomide, and dexamethasone (VRd) improved progression-free survival and complete-response rates in transplant-ineligible patients (the IMROZ trial), leading to approval in 2024; daratumumab-based quadruplets play a similar role in transplant-eligible patients. Anti-CD38 antibodies are also central to AL amyloidosis, where daratumumab added to bortezomib, cyclophosphamide, and dexamethasone markedly raised hematologic complete responses.
Relapsed and refractory disease
Several classes now compete here. Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, reduced the risk of progression or death by roughly three-quarters versus standard care in lenalidomide-refractory disease (the CARTITUDE-4 trial), and has moved into earlier lines. Belantamab mafodotin, a BCMA antibody-drug conjugate, produced superior progression-free survival when combined with bortezomib and dexamethasone versus a daratumumab triplet (about 37 versus 13 months in DREAMM-7); after an earlier market withdrawal, it was re-approved in 2025 on the strength of the DREAMM-7 and DREAMM-8 combination data (ocular toxicity remains its signature risk). Rounding out the options are the bispecific antibodies — the BCMA-directed teclistamab, elranatamab, and linvoseltamab, and the GPRC5D-directed talquetamab — which produce high response rates in triple-class-refractory disease at the cost of cytokine release syndrome and infection risk.
Further reading: IMROZ isatuximab-VRd (Facon et al., NEJM 2024); CARTITUDE-4 cilta-cel (San-Miguel et al., NEJM 2023); DREAMM-7 belantamab mafodotin (Hungria et al., NEJM 2024); ANDROMEDA daratumumab in AL amyloidosis (Kastritis et al., NEJM 2021).