On November 6, 2025, the U.S. Food and Drug Administration approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adults with high-risk smoldering multiple myeloma.
Efficacy of daratumumab and hyaluronidase as monotherapy vs active monitoring was evaluated in AQUILA, an open-label, randomized phase III trial in 390 patients with high-risk smoldering multiple myeloma. Patients randomly assigned to the treatment arm received daratumumab and hyaluronidase at 1,800 mg/30,000 units administered subcutaneously once weekly from weeks 1 to 8, once every 2 weeks from weeks 9 to 24, and once every 4 weeks starting with week 25 until 39 cycles or up to 36 months or until diagnosis of multiple myeloma or unacceptable toxicity.
Forty-one percent of patients had two or more of the following criteria for high-risk smoldering multiple myeloma: serum monoclonal protein level > 2 g/dL, involved-to-uninvolved serum-free light chain ratio > 20, and bone marrow plasma cells > 20%. Daratumumab and hyaluronidase is only indicated for patients with high-risk smoldering multiple myeloma. It is not indicated for other risk categories.
The major efficacy outcome measure of AQUILA was progression-free survival by independent review committee, defined as the diagnosis of multiple myeloma based on the International Myeloma Working Group diagnostic criteria for multiple myeloma or death. Median progression-free survival was not evaluable in the daratumumab and hyaluronidase arm and 41.5 months in the active monitoring arm (hazard ratio = 0.49; 95% confidence interval = 0.36–0.67; P < .0001).
The prescribing information for daratumumab and hyaluronidase includes warnings and precautions for hypersensitivity and other administration reactions, cardiac toxicity in patients with light chain amyloidosis, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching and red blood cell antibody screening.
The recommended dose is 1,800/30,000 units (daratumumab at 1,800 mg and 30,000 units hyaluronidase) administered subcutaneously over approximately 3 to 5 minutes.
