The U.S. Food and Drug Administration (FDA) has approved Darzalex Faspro (daratumumab and hyaluronidase-fihj, Janssen Biotech, Inc.) to treat adults with high-risk smoldering multiple myeloma (SMM). This is the first FDA approval for this category of patients at high risk of developing active multiple myeloma.
This was supported by the results of AQUILA (NCT03301220), an open-label study that randomized 390 patients with high-risk SMM. The participants were designated to active monitoring or the reception of daratumumab and hyaluronidase-fihj monotherapy. Participants of the treatment group were administered 1,800/30,000 units of the drug subcutaneously. The regimen was administered once a week in the first eight weeks, every two weeks in the next twenty-four weeks, and every four weeks starting with week twenty-five. The treatment was carried out up to 39 cycles or a total of about 36 months, or when the patient had progressed to multiple myeloma, or when the toxicity was unbearable.
The high-risk criteria used in the study were as follows: serum monoclonal protein levels greater than 2 g/dL, a ratio of involved to uninvolved serum-free light chains greater than 20, and bone marrow plasma cells greater than 20%. In the study, 41% of patients met at least two of the three high-risk criteria. The FDA stated that Darzalex Faspro is recommended for patients with high-risk SMM, not for other risk groups.
Progression-free survival (PFS) according to the International Myeloma Working Group (IMWG) diagnostic criteria was the primary efficacy endpoint of the study, as assessed by an independent review committee. The outcomes presented a substantial advantage of the daratumumab and hyaluronidase-fihj group. The median PFS was not achieved in the daratumumab and hyaluronidase-fihj group as compared with 41.5 months in the active monitoring group. The combining hazard ratio was 0.49, 95% confidence interval [CI]: 0.36 to 0.67, p < 0.0001.
The prescribing information lists potential risks, including interference with cross-matching and red blood cell antibody screening, embryo-fetal toxicity, neutropenia, thrombocytopenia, infections, cardiac toxicity in patients with light chain amyloidosis, and other administration-related reactions or hypersensitivity reactions. 1,800 mg of daratumumab and 30,000 units of hyaluronidase should be subcutaneously administered over a period of three to five minutes, respectively. The approval of Darzalex Faspro offers patients with high-risk SMM a significant new treatment option that may delay progression to active disease with the added convenience of subcutaneous administration.
Reference: USFDA. FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma. Published November 6, 2025, Accessed November 7, 2025. FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma
