Data presented at the ASH 2020 Annual Meeting & Exhibition showed that subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) significantly reduced risk of disease progression in patients with relapsed/refractory multiple myeloma (RRMM) compared with pomalidomide and dexamethasone alone.
Daratumumab (DARA) is an anti-CD38 antibody approved for the treatment of RRMM. A recently approved subcutaneous (SC) formulation has shown a similar safety profile to intravenous DARA, with a significant reduction in infection-related reactions (IRRs) and shorter administration time.
The phase III APOLLO study evaluated the addition of DARA SC to pomalidomide and dexamethasone (Pd) for treatment of RRMM that progressed following prior therapy. A total of 304 patients were randomized to Pd with or without DARA SC. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was improvement in progression-free survival (PFS).
Median treatment duration was 11.5 months for the D-PD cohort, compared with 6.6 months for Pd only. The overall hazard ratio (HR) was 0.63, or a 37% reduced risk of progression or death for patients treated with D-Pd (95% confidence interval [CI], 0.47-0.85; P=0.0018). Median PFS for D-Pd and Pd arms were 12.4 vs. 6.9 months, respectively. In the D-Pd group, 24.5% of patients achieved a complete response or better, compared with 3.9% for the Pd group. At a median 16.9 month follow-up, 99 patients (33%) died (HR, 0.91; 95% CI, 0.61-1.35). Survival data is still being collected and follow-up is ongoing.
The most common grade 3/4 adverse events (AEs) were neutropenia, leukopenia, lymphopenia, febrile neutropenia, and pneumonia. Rates of IRRs was 6% among the DARA SC group, with all events grade 1 or 2. Rates of treatment discontinuation due to AEs were similar between groups, and the safety profile of D-Pd is consistent with known profiles of both DARA SC and Pd alone.
“In this phase III study evaluating DARA SC plus Pd, D-Pd significantly reduced the risk of progression or death by 37% in patients with RRMM who had received ≥1 prior line of therapy vs Pd alone. No new safety concerns were observed. The IRR rate was very low and administration duration short, thus increasing convenience for patients and decreasing treatment burden,” the researchers concluded.