FDA Approves New Treatment for High-Risk Multiple Myeloma

On November 6, 2025, the FDA approved daratumumab and hyaluronidase-fihj, branded as Darzalex Faspro, for adults diagnosed with high-risk smoldering multiple myeloma. This treatment, developed by Janssen Biotech, Inc., marks a pivotal advancement in managing this precursor to multiple myeloma.

The approval is based on the results from the AQUILA trial, a randomized, open-label study involving 390 patients with high-risk smoldering multiple myeloma. Patients in the treatment group received daratumumab and hyaluronidase-fihj subcutaneously at a dosage of 1,800 mg and 30,000 units respectively, beginning weekly for the first two months, transitioning to biweekly, and finally to once every four weeks for up to 39 cycles or a maximum of 36 months.

The study defined high-risk smoldering multiple myeloma using criteria from the International Myeloma Working Group, where 41% of the participants met at least two of the following: a serum monoclonal protein level exceeding 2 g/dL, an involved-to-uninvolved serum-free light chain ratio over 20, and bone marrow plasma cells greater than 20%.

Primary efficacy was measured by progression-free survival, or PFS, assessed by an independent review committee. While the median PFS in the daratumumab and hyaluronidase-fihj group was not evaluable, the active monitoring arm showed a median PFS of 41.5 months.

The treatment demonstrated a significant reduction in the risk of progression to multiple myeloma, with a hazard ratio of 0.49 and a p-value less than 0.0001. Healthcare providers are advised to closely monitor for potential adverse effects, which include hypersensitivity reactions, cardiac toxicity in patients with light chain amyloidosis, and increased risk of infections and hematologic issues.

The prescribing information emphasizes that this therapy is specifically indicated for high-risk patients and is not to be used in other risk categories. This FDA approval not only provides a new therapeutic option for patients facing high-risk smoldering multiple myeloma but also underscores the ongoing innovations in genomic medicine and targeted therapies in oncology.

For further details, healthcare professionals can refer to Drugs@FDA for full prescribing information and reporting guidelines for adverse events. Follow updates from the FDA's Oncology Center of Excellence on X, formerly Twitter, at FDAOncology.