On November 6, 2025, the Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) for adults with high-risk smoldering multiple myeloma (SMM).
Complete prescribing information for Darzalex Faspro will be published in Drugs@FDA.
The 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 assigned 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 at week 25, until 39 cycles or until 36 months, or until diagnosis of multiple myeloma or unacceptable toxicity. 41% of patients had 2 or more of the following high-risk SMM criteria: serum monoclonal protein level >2 g/dL, involved/uninvolved serum free light chain ratio >20, and bone marrow plasma cells >20%. Darzalex Faspro is only indicated for patients with high-risk SMM. It is not indicated for other risk categories.
The primary efficacy measure was progression-free survival (PFS) assessed by an independent review committee (IRC), defined as diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria or death. Median PFS was not evaluable in the daratumumab and hyaluronidase-fihj arm and was 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-related reactions, cardiac toxicity in patients with light chain amyloidosis, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interference with crossmatch testing and red blood cell antibody detection.
The recommended dose is 1,800/30,000 units (1,800 mg of daratumumab and 30,000 units of 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 drug or device to the FDA MedWatch system or by calling 1-800-FDA-1088.
For assistance with single-patient IND applications for investigational oncology products, healthcare professionals can contact Project Facilitate of the Office of Oncology Excellence (OCE) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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Information from FDA