FDA Grants Approval to Daratumumab and Hyaluronidase for High-Risk Smoldering MM
On November 6 2025, the US Food and Drug Administration (FDA) granted approval to daratumumab and hyaluronidase-fihj (Darzalex Faspro) for the treatment of patients with high-risk smoldering multiple myeloma (SMM).
To support this approval, the efficacy of daratumumab and hyaluronidase-fihj as monotherapy versus active monitoring was evaluated in the AQUILA trial. This trial was an open-label, randomized trial including 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.
Within this trial, 41% 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%.
An independent review committee assessed the major efficacy outcome measure of progression-free survival (PFS), 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 was 41.5 months in the active monitoring arm (hazard ratio [HR], 0.49; [95% confidence interval [CI], 0.36 to 0.67; P <0.0001).
Daratumumab and hyaluronidase-fihjis is currently only indicated for patients with high-risk smoldering multiple myeloma, and not for other risk categories.
Warnings and precautions for prescribing daratumumab and hyaluronidase-fihj include 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
Source:
US Food and Drug Administration. Accessed November 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma
