Phase 3 isatuximab (anti-CD38 mAb) + iberdomide (CRBN E3 ligase modulator) in transplant-eligible NDMM

Dana-Farber Cancer Institute’s randomized DETERMINATION 2 program tests whether a risk- and MRD/response-adapted strategy can improve outcomes for newly diagnosed, transplant-eligible multiple myeloma. Everyone starts with 8 induction cycles of isatuximab (Sanofi; CD38-directed monoclonal antibody with immune-mediated and direct myeloma-cell killing) plus iberdomide (Bristol Myers Squibb/Celgene; next-generation IMiD/CELMoD that binds cereblon to drive degradation of transcription factors such as Ikaros/Aiolos), alongside bortezomib (Takeda; 26S proteasome inhibitor) and dexamethasone (glucocorticoid). After induction, patients are assigned by end-of-induction response/MRD and risk: some go into prolonged isatuximab+iberdomide maintenance with later de-escalation/escalation, while higher-risk/less-deep responders enter Cohort 2 where consolidation is either high-dose melphalan with autologous transplant (the comparator approach) or linvoseltamab (Regeneron; BCMA×CD3 bispecific T-cell engager) consolidation followed by isatuximab+iberdomide maintenance. The core scientific/commercial angle is moving a BCMA bispecific and a CELMoD into front-line, transplant-eligible care while explicitly using MRD to individualize intensity; today’s care for this population is triplet/quad induction (often VRd- or daratumumab-based), stem-cell collection with many patients proceeding to early autologous transplant, then lenalidomide-based maintenance with additions for higher-risk disease.