APOLLO: Combination of Daratumumab + Pomalidomide and Dexamethasone versus Pomalidomide and Dexamethasone Alone in Patients with RRMM

Conference Correspondent —December 16, 2020

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.


Reference

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).

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Last modified: December 16, 2020

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