The FDA has approved Daratumumab and Hyaluronidase-fihj (Darzalex Faspro) for the treatment of adult patients with high-risk smoldering multiple myeloma (SMM) — marking the first approved therapy for this early disease stage.
Approval Basis – AQUILA Trial (NCT03301220):
The open-label Phase 3 trial enrolled nearly 390 patients randomized to subcutaneous daratumumab versus active monitoring. Daratumumab was administered weekly for 8 weeks, every 2 weeks through week 24, then every 4 weeks up to 39 cycles or until progression.
Efficacy:
Median progression-free survival (PFS) was not reached with daratumumab vs 41.5 months with observation (HR 0.49; p < 0.0001). 5-year PFS: 63% vs 41%. Overall response rate: 63% vs 2%. 5-year overall survival: 93% vs 87%.
Safety:
Adverse events were consistent with prior daratumumab experience. The most common included infections, fatigue, musculoskeletal pain, rash, and injection-site reactions. Grade 3–4 events occurred in ~40% of patients.
Clinical Significance:
This approval introduces a new standard for early intervention in high-risk SMM, offering patients a strategy to delay progression to symptomatic myeloma with a well-characterized safety profile.