Daratumumab in Combination with Carfilzomib, Lenalidomide, and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma (MMY1001): An Open-Label Phase 1b Study
Daratumumab (DARA) is a CD38-directed monoclonal antibody that is indicated for use in patients with newly diagnosed multiple myeloma (MM) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone. DARA in combination with established standard-of-care regimens has been shown to prolong progression-free survival (PFS), and demonstrates a favorable safety profile in relapsed or refractory MM. In this study, researchers examined the efficacy and tolerability of DARA in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients newly diagnosed with MM.
For study inclusion, patients were to be newly diagnosed, regardless of transplantation eligibility. Patients were randomized to receive DARA 16 mg/kg once weekly for cycles 1 and 2, once every 2 weeks for cycles 3 to 6, and once every 4 weeks for the remainder of the study. Carfilzomib 20 mg/m2 was administered on cycle 1, day 1, and was subsequently escalated to 70 mg/m2. Carfilzomib was given on days 1, 8, and 15 of each 28-day cycle for ≤13 cycles or discontinuation for autologous stem-cell transplant (ASCT). Lenalidomide 25 mg was administered on days 1 to 21 and dexamethasone 20 mg to 40 mg was given every week.
The 22 patients enrolled in this study received a median of 11.5 treatment cycles. Patients were monitored for a median duration of 10.8 months. Treatment with DARA-KRd yielded an overall response rate (≥partial response) of 100% in 21 response-evaluable patients, including 9 patients (43%) who achieved complete response (best response). This combination also showed a 12-month PFS rate of 94%.
Serious adverse events occurred in 46% of patients, and 14% were possibly related to DARA. The most common grade 3/4 treatment-emergent adverse events (TEAEs; >10%) reported were lymphopenia (64%) and neutropenia (15%). No grade 5 TEAEs were reported. Eight (36%) patients discontinued treatment—1 due to an adverse event (pulmonary embolism), 1 due to disease progression, and 6 due to ASCT.
The combination of DARA and KRd was well-tolerated, and the overall safety profile was consistent with previous studies. No additional toxicity was reported with the inclusion of DARA. One patient each experienced tachycardia, congestive heart failure, and hypertension, respectively. No grade 3 or 4 infusion reactions were reported. These data support further studies to examine the DARA-KRd combination as a frontline treatment regimen in patients with newly diagnosed MM.
Jakubowiak AJ, et al. ASCO Abstract 8000.