Phase 1b/2 isatuximab + iberdomide cereblon E3-ligase modulator combo in NDMM

Dana-Farber Cancer Institute is running this Phase 1b/2, open-label study testing a four-drug induction regimen—isatuximab (Sanofi; CD38-directed monoclonal antibody), iberdomide (Bristol Myers Squibb/Celgene; cereblon E3 ligase modulator that drives degradation of Ikaros/Aiolos), bortezomib (Takeda; 26S proteasome inhibitor), and dexamethasone (glucocorticoid)—followed by maintenance for participants achieving at least a partial response after 8 cycles. The trial focuses on newly diagnosed multiple myeloma patients who are transplant-ineligible or not planned for upfront transplant, with two pragmatic intensity strata: Arm A (<70 and fit) uses a standard-intensity bortezomib/dexamethasone schedule, while Arm B (≥70 and/or intermediate fit/frail) uses reduced-intensity dosing and continues bortezomib into maintenance. A key scientific angle is substituting a next-generation cereblon modulator (iberdomide) into a CD38-antibody–based frontline backbone to deepen responses (including MRD negativity) while tuning tolerability for older/frail patients. Today’s care for transplant-ineligible NDMM commonly uses daratumumab- or isatuximab-based combinations such as DRd or D-VMP/Isa-VRd in some settings, or VRd/other triplets in fit patients, with dose-attenuated regimens for frailty—this study explores whether a cereblon-modulator quadruplet can improve depth and durability without forcing transplant-level intensity.