Daratumumab plus Pomalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Results of a 4-Arm Phase 1b Study
Daratumumab is a human anti-CD38 monoclonal antibody that was recently approved as monotherapy for the treatment of heavily treated patients with relapsed and refractory multiple myeloma (RRMM).1 Ongoing studies are evaluating daratumumab as combination therapy with different backbone therapies, including lenalidomide/dexamethasone (Len/Dex) in patients with RRMM.2 At the 2015 ASH meeting, Chari and colleagues presented results of a 4-arm phase 1b study that evaluated the safety and efficacy of daratumumab in combination with pomalidomide and dexamethasone (Pom/Dex).3
A total of 77 patients were enrolled in the trial and had received a median of 3.5 (2-10) prior therapies; 56% of patients were refractory to bortezomib, 30% to carfilzomib, 88% to lenalidomide, and 65% to both a proteasome inhibitor and an immunomodulatory drug. Patients received daratumumab 16 mg/kg weekly for 2 cycles, then every 2 weeks for 4 cycles, and every 4 weeks until disease progression; pomalidomide 4 mg was administered daily for 21 days and dexamethasone 40 or 20 mg weekly. Of the 28 patients who discontinued study treatment, 15 (20%) were due to progressive disease and 6 (8%) were due to adverse events (AEs). Daratumumab-specific infusion-related reactions occurred in 47 patients, and included chills (13%), cough (13%), and dyspnea (11%). Grade 3/4 AEs were mostly hematologic, including neutropenia (51%), anemia (21%), leukopenia (16%), and thrombocytopenia (10%); nonhematologic grade 3/4 AEs included dyspnea (6.5%), hypertension (5%), and fatigue (5%). Five deaths were reported, 4 due to AEs and 1 due to progressive disease. In terms of antitumor response, the overall response rate (ORR) was 58.5% in the 53 patients who had >1 postbaseline assessments, with 3 stringent complete responses (sCRs), 1 complete response (CR), 12 very good partial responses (VGPRs), and 15 partial responses (PRs); in many cases, an increase in depth of response was observed over time. Among the 40 evaluable double-refractory patients, an ORR of 57% was achieved, including 1 sCR, 1 CR, 10 VGPRs, and 11 PRs. Overall, the addition of daratumumab to Pom/Dex did not result in unexpected or exacerbate known Pom/Dex toxicities, while yielding high response rates.
- Darzalex (daratumumab) [Prescribing information]; 2015.
- Plesner T, et al. Blood. 2014;124(21):84.
- Chari A, et al. ASH 2015. Abstract 508.