Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR

Abstract

Background: Daratumumab (D), a human antiCD38 IgG mAb, induces deep and durable responses with a favorable safety profile in RRMM pts. We report a prespecified interim analysis of the first randomized controlled study of D (CASTOR; NCT02136134 ). Method(s): Pts with 1 prior line of therapy were randomized (1:1) to 8 cycles (q3w) of bortezomib (V)/dexamethasone (d) (V: 1.3 mg/m2sc on Days 1, 4, 8, 11; d: 20 mg po on Days 1, 2, 4, 5, 8, 9, 11, 12) +/- D (16 mg/kg iv qw in Cycles 13, Day 1 of Cycles 48, then q4w until progression). Primary endpoint was PFS. Result(s): 498 pts (DVd, 251; Vd, 247) were randomized. Baseline demographics and disease characteristics were well balanced. Pts received a median of 2 prior lines of therapy (range 110). 66% received prior V; 76% received prior IMiD; 48% received prior PI and IMiD; 33% were IMiDrefractory; 32% were refractory to last line of prior therapy. With median followup of 7.4 months, D significantly improved median PFS (61% reduction in risk of progression) and TTP for DVd vs Vd (Table). D significantly increased ORR (83% vs 63%, P <0.0001), and doubled rates of VGPR (59% vs 29%, P <0.0001), and CR (19% vs 9%, P= 0.0012) for DVd vs Vd, respectively; median duration of response was NR vs 7.9 months, respectively. Most common (>25%) AEs (DVd/Vd) were thrombocytopenia (59%/44%), peripheral sensory neuropathy (47%/ 38%), diarrhea (32%/22%) and anemia (26%/31%). Most common grade 3/4 AEs (>10%) were thrombocytopenia (45%/33%), anemia (14%/16%), neutropenia (13%/4%). 7%/9% of pts discontinued due to a TEAE. Dassociated infusionrelated reactions (45% of pts) mostly occurred during the first infusion; most were grade 1/2 (grade 3/4, 9%/0%). Conclusion(s): D significantly improved PFS, TTP, and ORR in combination with Vd vs Vd alone. DVd doubled both VGPR and sCR/CR rates vs Vd alone. Safety of DVd is consistent with the known safety profile of D and Vd. The addition of D to Vd should be considered a new standard of care for RRMM pts currently receiving Vd alone.