On November 6, 2025, the Food and Drug Administration approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) for adults with high-risk smoldering multiple myeloma (SMM).

Full prescribing information for Darzalex Faspro will be posted on Drugs@FDA.

Efficacy of daratumumab and hyaluronidase-fihj as monotherapy versus active monitoring was evaluated in AQUILA (NCT03301220), an open-label, randomized trial in 390 patients with high-risk SMM. Patients randomized to the treatment arm received daratumumab and hyaluronidase-fihj 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 to multiple myeloma or unacceptable toxicity. Forty-one percent of patients had 2 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%. Darzalex Faspro is only indicated for patients with high-risk smoldering multiple myeloma. It is not indicated for other risk categories.

The major efficacy outcome measure was progression-free survival (PFS) by independent review committee (IRC) as defined as the diagnosis of multiple myeloma based on the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma or death. Median PFS was not evaluable in the daratumumab and hyaluronidase-fihj arm and 41.5 months in the active monitoring arm (Hazard ratio 0.49 [95% CI: 0.36-0.67]; p-value <0.0001).

The prescribing information for daratumumab and hyaluronidase-fihj 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 (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3 to 5 minutes.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X: @FDAOncology.