A Phase II Study of Daratumumab in Combination with Bortezomib and Dexamethasone in Patients with Multiple Myeloma Who Received One Prior Line of Therapy (KMM1906).

Purpose: Daratumumab combined with bortezomib and dexamethasone (DVd) has been established as the standard treatment for relapsed/refractory multiple myeloma (MM) based on pivotal phase 3 trials. A subgroup analysis demonstrated enhanced efficacy in the second-line setting, although the fixed duration of bortezomib administration remained a limitation. Therefore, we conducted a phase II trial evaluating continuous bortezomib as maintenance in a DVd regimen for second-line treatment.

Materials And Methods: This phase II study (KCT0004352) enrolled patients with MM receiving second-line DVd therapy: daratumumab (16 mg/kg IV, weekly for cycles 1-3, every 3 weeks for cycles 4-8, every 4 weeks thereafter), bortezomib (1.3 mg/m² SQ, twice weekly for cycles 1-8, biweekly thereafter), and dexamethasone (20 mg IV or PO on treatment days), as in the pivotal trial. After nine cycles, daratumumab and bortezomib were continued until progression or unacceptable toxicity. The primary endpoint was a ≥ very good partial response (VGPR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and minimal residual disease (MRD) negativity assessed by EuroFlow-based next-generation flow in bone marrow.

Results: Between June 2020 and 2021, 26 patients (median age 72) from 10 Korean centers were enrolled. All had one prior treatment line; 73% had prior bortezomib, and 69% had prior immunomodulators. At a median follow-up of 25.4 months, 65% discontinued due to progression, death, or withdrawal. VGPR or better was achieved in 65%, with 23% MRD-negative. Median PFS was 21.8 months; OS was not reached. The 24-month OS rate was 69.2%. Grade 3 adverse events included thrombocytopenia and lymphopenia; 31% had serious AEs, and 65% required dose modifications.

Conclusion: Continuous DVd therapy showed promising efficacy and manageable toxicity as a second-line option.