FDA Alert

FDA Approves Daratumumab, Hyaluronidase-Fihj for High-Risk Smoldering Multiple Myeloma After Promising Efficacy Data

Kate Young

Key Highlights

  • The FDA approved daratumumab and hyaluronidase-fihj for adults with high-risk smoldering multiple myeloma.
  • Data from the AQUILA trial found that the treatment improves the risk of disease progression and death.
  • The most common adverse reaction is hypertension, and the study authors reported no unexpected safety concerns.

On Nov. 6, 2025, the FDA approved daratumumab and hyaluronidase-fihj for adults with high-risk smoldering multiple myeloma (SMM) following data from the AQUILA trial.1

The open-label, randomized trial enrolled 390 patients with high-risk SMM, who were randomized to an active monitoring arm and a treatment arm that received 1800 mg/30,000 units of daratumumab and hyaluronidase-fihj subcutaneously. The treatment was initially administered once weekly from weeks 1 to 8 before shifting to once very 2 weeks for weeks 9 to 24 and once very 4 weeks for weeks 25 until 39 cycles.2  

The researchers measured efficacy by progression-free survival (PFS) according to the International Myeloma Working Group criteria or death.1,2 Secondary outcome measures included time to biochemical or diagnositic progression, overall response rate, complete response rate, time to first-line treatment for multiple myeloma, progression-free survival on first line treatment for multiple myeloma, and overall survival.2

The researchers found that the risk of disease progression or death was 51% lower in the daratumumab arm than the active monitoring arm (P < .001). Progression-free survival at 5 years was 63.1% in the daratumumab arm versus 40.8% in the active monitoring arm, and overall survival at 5 years was 93% and 86.9% respectively.3

The most common adverse event in both groups was hypertension (5.7% vs. 4.6%), and 5.7% of the treatment arm discontinued treatment as a result of adverse events.3

“Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring,” the researchers concluded in the study. “No unexpected safety concerns were identified.”

The FDA advises that the recommended dose is 1800/30,000 units to be administered subcutaneously over 3 to 5 minutes and warns of clinicians to take precautions for hypersensitivity and other administration reactions.1

References

  1. FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma. Published Nov. 6, 2025. Accessed Nov. 19, 2025.
  2. A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants with High-Risk Smoldering Multiple Myeloma. https://clinicaltrials.gov/study/NCT03301220. Published Nov. 10, 2025. Accessed Nov. 19, 2025.
  3. Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. N Engl J Med. 2025;392(18):1777-1788. doi:10.1056/NEJMoa2409029