Daratumumab (CD38) + ixazomib (oral proteasome inhibitor) sans dexamethasone delivers 19.5-mo PFS in frail elderly RRMM

Daratumumab is an anti-CD38 monoclonal antibody and ixazomib is an oral proteasome inhibitor; IFM 2018-02 (NCT03757221) tested this dexamethasone-free doublet (with methylprednisolone premedication) in a prospective Phase 2, multicenter French study for frail relapsed/refractory multiple myeloma in 1st/2nd relapse (n=55; median age 82, 90%>75; IMWG frailty score ≥2; ECOG 0–2). The primary endpoint (≥VGPR) was met in 32%, with median PFS 19.5 months at 35.3 months’ median follow-up and OS not reached (75% alive at 33.6 months). Grade ≥3 AEs occurred in 67% (notably cytopenias [n=18] and infections [n=8], including 6 pneumonias)—with efficacy that looks broadly in-range for standard relapse triplets like IRd (ixazomib-lenalidomide-dexamethasone) where median PFS was ~20.6 vs 14.7 months in TOURMALINE-MM1, and D-Pd (daratumumab-pomalidomide-dexamethasone) where median PFS was 12.4 vs 6.9 months in APOLLO, but achieved here in a much older, explicitly frail cohort and without chronic dexamethasone.