Multiple Myeloma: Treatment

Multiple Myeloma: overview

This algorithm addresses newly diagnosed multiple myeloma, with transplant eligibility as the first branch point, followed by relapsed or refractory disease. For transplant-eligible patients, the chart shows quadruplet induction with Dara-VRd followed by autologous stem cell transplant (PERSEUS), then lenalidomide maintenance. In the site's PERSEUS summary, D-VRd improved 4-year PFS (84% vs 68%, HR 0.42) and more than doubled sustained MRD negativity compared with VRd, establishing it as the standard quadruplet induction in this setting.

For transplant-ineligible patients, the triplet options are Dara-Rd (MAIA) and VRd (SWOG S0777). MAIA showed that adding daratumumab to lenalidomide and dexamethasone prolonged PFS and OS, with higher MRD-negativity rates. At relapse, the chart lists a triplet selected according to prior drug exposure (POLLUX and CASTOR), BCMA-directed CAR-T therapy with cilta-cel or ide-cel (CARTITUDE-4), and the bispecific antibodies teclistamab or talquetamab.

Trials behind this algorithm

PERSEUS Sonneveld P et al, NEJM, 2024; PMID: 38084760
MAIA Facon T et al, NEJM, 2019; PMID: 31141632
POLLUX Trial Bahlis et al, Leukemia, 2020, PMID: 32001798
CARTITUDE-4 San-Miguel J et al, NEJM, 2023; PMID: 37272512
TECLISTAMAB + DARATUMUMAB Costa LJ et al, NEJM, 2025; PMID: 41363801

Background reading: Multiple myeloma, MGUS, and smoldering myeloma board review notes.

Multiple Myeloma: the algorithm in words

Starting point: Multiple myeloma (newly diagnosed). Full background: Multiple myeloma, MGUS, and smoldering myeloma notes.

Transplant-eligible (first-line): Quadruplet: Dara-VRd → autologous SCT (PERSEUS); Maintenance: Lenalidomide maintenance (post-transplant).
Transplant-ineligible (first-line): Triplet: Dara-Rd (MAIA); Triplet: VRd (SWOG S0777).
Relapsed / refractory (second-line): Triplet: Triplet by prior exposure (POLLUX / CASTOR); BCMA CAR-T: Cilta-cel / ide-cel (CARTITUDE-4); BiTE: Teclistamab / talquetamab (bispecific).