SC daratumumab monotherapy for the treatment of high-risk smoldering MM

Daratumumab, an anti-CD38 monoclonal antibody, is a standard-of-care therapy for the treatment of patients with MM. However, evidence on its applications in patients with high-risk SMM remains limited.¹

Results from the randomized, phase III AQUILA study (NCT03301220), evaluating the efficacy and safety of SC daratumumab monotherapy in patients with high-risk SMM, aiming to delay progression to active MM, were published by Dimopoulos et al. in The New England Journal of Medicine.¹ A total of 390 patients with high-risk SMM were enrolled across 23 countries and received either SC daratumumab 1,800 mg (n = 194) or active monitoring (n = 196). The primary end point was PFS, which was evaluated in an analysis of time from randomization to initial documentation of disease progression to active MM or death from any cause – whichever occurred first.¹

Key learnings¹

Daratumumab significantly reduced the risk of progression to active MM or death by 51% vs active monitoring (HR: 0.49; 95% CI: 0.36–0.67; p < 0.001). The 5-year PFS rate was 63.1% with daratumumab vs 40.8% with active monitoring, with OS rates of 93.0% vs 86.9%.

Initiation of first-line therapy for active MM was required in 33.2% of patients in the daratumumab group vs 53.6% in the active monitoring group.

Grade 3/4 AEs occurred in 40.4% of patients treated with daratumumab vs 30.1% with active monitoring, with hypertension being the most common. Serious AEs were reported in 29.0% and 19.4% of patients, respectively, and 5.7% of patients in the daratumumab group required treatment discontinuation.

Subcutaneous daratumumab monotherapy was associated with a significantly reduced risk of progression to active MM or death, with higher OS rates, vs active monitoring in patients with high-risk smoldering MM, with no unexpected safety concerns identified.