FDA Approves Darzalex Faspro in High-Risk Smoldering Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has approved Darzalex Faspro (daratumumab and hyaluronidase-fihj) for the treatment of adults with high-risk smoldering multiple myeloma.

The approval was announced in a notice issued by the agency.

The effectiveness of the treatment as a monotherapy versus active monitoring was determined in the open-label, randomized AQUILA clinical trial of 390 patients with high-risk smoldering multiple myeloma. Patients in the experimental arm received the treatment as 1,800 milligrams/30,000 unites subcutaneously, meaning under the skin, once a week from week 1 through 8, then every two weeks from weeks 9 to 24 and once every four weeks from week 25 until 39 cycles or up to 36 months or until diagnosis of multiple myeloma or unacceptable toxicity.

Median progression-free survival was not evaluable in the experimental arm and 41.5 months in the active monitoring arm.

The prescribing information for the treatment, as stated by the FDA, includes warnings and precautions for 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.

The recommended dose, according to the agency, is 1,800/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately three to five minutes.

More From the AQUILA Study

A poster presented earlier this year at the 2025 Society of Hematologic Oncology Annual Meeting showed that subcutaneous Darzalex Faspro showed that, with a median follow-up of 65.2 months and the median progression-free survival not reached with Darzalex Faspro versus 41.5 months with monitoring, there was a 51% reduction in the risk of progressive disease or death.

“Darzalex Faspro demonstrated a favorable safety profile, with a low rate (5.7%) of treatment discontinuation due to treatment-emergent side effects. Patients maintained their health-related quality of life during Darzalex Faspro treatment compared with active monitoring,” lead study author, Dr. Meletios Athanasios Dimopoulos, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece, wrote in the poster with coauthors.

“Results from the phase 3 AQUILA study strongly support early intervention with subcutaneous Darzalex Faspro monotherapy for a fixed duration in patients with high-risk smoldering multiple myeloma, representing an opportunity to delay or avoid end-organ damage and progression to multiple myeloma although preserving quality of life and extending survival.”

Data showed an objective response rate of 63.4% with Darzalex Faspro versus 2% with active monitoring. Among patients who received Darzalex Faspro, a very good partial response or better occurred in 29.9%, and 8.8% had a complete response or better.

The median time to initiating subsequent frontline therapy was not reached in the Darzalex Faspro arm and 50.2 months in the monitoring arm. The 60-month progression-free survival rate on frontline therapy was 85.9% and 78% in each respective arm. The 60-month overall survival rates were 93% and 86.9%, respectively.

Investigators noted no new safety signals among those who received Darzalex Faspro. In the Darzalex Faspro and monitoring arms, 96.9% versus 82.7% had side effects of any grade, 40.4% versus 30.1% had grade 3 (severe) or higher side effects, 29% versus 19.4% had serious side effects, and 1% versus 2% had grade 5 (fatal) side effects. The most common grade 3 or higher side effect in each arm was hypertension (5.7% versus 4.6%), and the incidence of second primary malignancies was comparable between arms (9.3% versus 10.2%).

References

1. “FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma,” FDA; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-high-risk-smoldering-multiple-myeloma
2. “Subcutaneous Darzalex Faspro Extends PFS in Smoldering Myeloma,” CURE; https://www.curetoday.com/view/subcutaneous-darzalex-faspro-extends-pfs-in-smoldering-myeloma

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