This primary analysis evaluated patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior lines of therapy, including lenalidomide (Len) and a proteasome inhibitor (PI). Compared with pomalidomide and dexamethasone (Pd) alone, daratumumab (DARA) plus Pd reduced the risk of disease progression and death without additional safety signals.
The APOLLO study objective was to evaluate DARA (subcutaneous) plus Pd versus Pd alone in patients with RRMM who had received ≥1 prior lines of therapy, including Len and a PI. Data reported here are from the primary analysis.
Patients with RRMM were eligible for this open-label study if they received ≥1 prior lines of therapy, including Len and a PI (patients with only 1 prior line of therapy were required to be refractory to Len), and had responded to prior treatment and progressed on or after their last regimen. Patients could not have previously taken anti-CD38 or Pd and were randomized 1:1; stratification was based on the International Staging System (ISS) disease stage and number of prior lines of therapy.
Treatment cycles 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. Patients in the DARA-Pd arm received DARA once weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and every 4 weeks thereafter. Initially, patients received DARA intravenously (16 mg/kg; N = 7). However, after protocol amendment, DARA was received subcutaneously 1800 mg co-formulated with recombinant human hyaluronidase PH20 (Halozyme, Inc). Treatment continued until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS); secondary end points 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.
In this study, 304 patients were randomized 1:1 to DARA-Pd (N = 151) or Pd (N = 153). Median age was 67 years (range, 35-90 years). ISS stage distribution was I (45%), II (33%), and III (22%). In 35% of patients, the presence of del17p, t(14;16), or t(4;14) was identified, classifying patients as high cytogenetic risk; 11% of patients received 1 prior line of therapy (median, 2; range, 1-5); 79.6% refractory to Len, 48.0% refractory to a PI, and 42.4% refractory to both. Median treatment duration was 11.5 months (DARA-Pd) versus 6.6 months (Pd).
There was a 37% reduction in the risk of progression or death in patients in the DARA-Pd arm at primary analysis, which means that the study met the primary end point of improved PFS (hazard ratio, 0.63; 95% confidence interval, 0.47-0.85; P = .0018). Median PFS was 12.4 versus 6.9 months for the DARA-Pd and Pd arms, respectively. At median follow-up of 16.9 months, 99 (33%) patients died; survival data are immature. In the DARA-Pd arm, 24.5% of patients achieved ≥CR and 51.0% achieved ≥VGPR. In the Pd arm, 3.9% of patients achieved ≥CR and 19.6% achieved ≥VGPR.
Based on a ≥5% difference between arms (DARA-Pd vs Pd), the most common grade 3/4 adverse events were neutropenia (68% vs 51%), leukopenia (17% vs 5%), lymphopenia (12% vs 3%), febrile neutropenia (9% vs 3%), and pneumonia (13% vs 7%). When DARA was given subcutaneously, the rate of injection-related reactions was low (6%) and were all grade 1/2. In 2% of patients, grade 1 local injection-site reactions occurred. Discontinuation rates due to treatment-emergent adverse events were similar between arms (2% DARA-Pd vs 3% Pd).
The risk of disease progression or death was reduced significantly by 37% with DARA-Pd for this patient population when compared with Pd. No new safety signals were observed. Patient burden was decreased by the low rate of injection-related reactions and the short administration time (median, 5 minutes) associated with subcutaneous delivery of DARA, which makes DARA-Pd an effective and convenient therapy for patients with RRMM who received ≥1 prior therapies, 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).