Delaying Progression from Smoldering to Active Multiple Myeloma

Daratumumab is an anti-CD38 monoclonal antibody approved for treatment of active multiple myeloma. Smoldering myeloma, defined as monoclonal protein ≥3g/L, urine paraprotein ≥500 mg/24 hours, and/or marrow plasmacytosis of 10%–59% in the absence of myeloma-defining events, has a variable time course to progression to overt myeloma and initiation of therapy.

In the industry-sponsored, multicenter, phase 3 AQUILA trial, 390 patients with smoldering myeloma at high risk for progression to active myeloma were randomized to subcutaneous daratumumab (1800 mg subcutaneously for 39 cycles, 36 months, or until progression) or scheduled monitoring without therapy.

During a median 65-months' follow-up, the daratumumab group had a significantly lower risk of progression or death relative to the monitoring group (hazard ratio, 0.49). At 5 years, rates of progression-free survival (PFS), the primary endpoint, were 63% and 41%, respectively. Five-year overall survival also was better with daratumumab (93% vs. 87%). Serious adverse events occurred in 29% with daratumumab and 19% with monitoring; grade 3–4 infections were higher with daratumumab (16.1% vs. 4.6%). Patient-reported outcomes were similar in the two groups.