FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma

FDA approval (Nov 6, 2025)

The US Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech, Inc.) for adults with high-risk smoldering multiple myeloma (SMM).

The FDA noted Darzalex Faspro is only indicated for patients with high-risk SMM and not indicated for other risk categories. Full prescribing information will be posted on Drugs@FDA.

Supporting trial: AQUILA (NCT03301220)

Efficacy was evaluated in AQUILA, an open-label, randomized trial in 390 patients with high-risk SMM comparing daratumumab/hyaluronidase-fihj monotherapy vs active monitoring.

Dosing in AQUILA: 1,800 mg/30,000 units subcutaneously once weekly (weeks 1–8), every 2 weeks (weeks 9–24), then every 4 weeks starting week 25, until 39 cycles (up to 36 months) or until diagnosis of multiple myeloma or unacceptable toxicity.

High-risk features: 41% had ≥2 of: serum monoclonal protein >2 g/dL, involved-to-uninvolved serum-free light chain ratio >20, bone marrow plasma cells >20%.

Primary endpoint (IRC-assessed PFS): progression to multiple myeloma per IMWG criteria or death. Median PFS was not evaluable in the treatment arm vs 41.5 months with active monitoring (HR 0.49; 95% CI 0.36–0.67; p<0.0001).

Label safety highlights

Warnings/precautions include hypersensitivity/administration reactions, cardiac toxicity in patients with light chain amyloidosis, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with cross-matching/RBC antibody screening.

Recommended dose: 1,800/30,000 units SC over ~3–5 minutes.