The authors of the APOLLO study aimed to evaluate the combination of daratumumab (DARA; subcutaneous) + pomalidomide and dexamethasone (Pd) versus Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior lines of therapy, including lenalidomide (Len) and a proteasome inhibitor (PI). The data presented here are from the primary analysis.
Patients were eligible for this study if they had received ≥1 prior lines of therapy, had responded to prior treatment, and progressed on or after their last regimen. Patients were not eligible if they had previously taken an anti-CD38 agent or Pd. Patients were randomized 1:1, and stratification was based on the International Staging System (ISS) disease stage and number of prior lines of therapy.
Treatment cycles in the study were 28 days. Patients received pomalidomide 4 mg once daily on days 1 to 21 and dexamethasone 40 mg on days 1, 8, 15, and 22. In the DARA-Pd arm, DARA was given once weekly for cycles 1 and 2, once every 2 weeks for cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression (DP) or unacceptable toxicity. Progression-free survival (PFS) was the primary end point. Secondary end points in the trial included overall response rate, rates of very good partial response or better (≥VGPR) and complete response or better (≥CR), minimal residual disease–negativity rate, overall survival, and safety.
A total of 304 patients were randomized 1:1 to DARA-Pd (n = 151) or Pd alone (n = 153). The median age for patients was 67 years (range, 35-90 years). ISS stage distribution was 45% in stage I, 33% in stage II, and 22% in stage III. Thirty-five percent of patients were classified as high cytogenetic risk. A total of 79.6% of patients were refractory to Len, 48.0% of patients were refractory to a PI, and 42.4% of patients were refractory to both. Median duration of treatment in the DARA-Pd arm was 11.5 months versus 6.6 months in the Pd arm.
There was a 37% reduction of risk for progression or death in patients observed in the DARA-Pd arm compared with the Pd arm. The study met its primary end point of improved PFS (hazard ratio, 0.63; 95% confidence interval, 0.47-0.85; P = .0018). Median PFS was 12.4 months versus 6.9 months for the DARA-Pd and Pd arms, respectively. The survival data are still immature. In the DARA-Pd arm, 24.5% of patients achieved ≥CR and 51.0% achieved ≥VGPR, compared with patients in the Pd arm, where 3.9% of patients achieved ≥CR and 19.6% achieved ≥VGPR.
The most common grade 3/4 adverse events (AEs) were neutropenia (68% vs 51%), leukopenia (17% vs 5%), lymphopenia (12% vs 3%), febrile neutropenia (9% vs 3%), and pneumonia (13% vs 7%). The rate of injection-related reactions for DARA was low (5%) and all were grade 1/2. Grade 1 local injection-site reactions occurred in 2% of patients. Discontinuations because of treatment-emergent AEs were similar between both treatment arms.
DARA-Pd significantly reduced the risk for DP or death by 37% for this patient population versus Pd. No new safety signals were observed. Patients experienced a low rate of injection-related reactions. The short administration time (median, 5 minutes) associated with subcutaneous delivery of DARA decreases the patient burden. DARA-Pd is an effective and convenient therapy for patients with RRMM who received ≥1 prior lines of therapy, including Len and a PI.
Abstract 412. ASH 2020. December 4, 2020. APOLLO: Phase 3 Randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients (Pts) with relapsed/refractory multiple myeloma (RRMM).