On July 30, 2024, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro®) in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantations (ASCT).
Efficacy was evaluated in PERSEUS (NCT03710603), an open-label, randomized, active-controlled trial in patients with newly diagnosed multiple myeloma who are eligible for ASCT. Enrollment was limited to patients aged 70 years or younger. A total of 709 patients were randomized to the daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone (daratumumab and hyaluronidase-fihj–VRd) arm (n = 355) and the bortezomib, lenalidomide, and dexamethasone (VRd) arm (n = 354).
The major efficacy outcome measure was progression-free survival (PFS) as assessed by an independent review committee based on International Myeloma Working Group response criteria. PERSEUS demonstrated an improvement in PFS in the daratumumab and hyaluronidase-fihj–VRd arm as compared to the VRd arm. At the time of this report, the median PFS had not been reached in either arm; however, treatment with daratumumab and hyaluronidase-fihj–VRd resulted in a reduction in the risk of disease progression or death by 60% compared to VRd alone (HR [95% CI] = 0.40 [0.29, 0.57]; p < 0.0001).
The most common adverse reactions reported in at least 20% of patients in the PERSUS trial were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended daratumumab and hyaluronidase-fihj dose is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase). See the full prescribing information on Drugs@FDA for the dosage recommendations for the other drugs.
The applicant used the Assessment Aid, a voluntary submission to facilitate the FDA’s assessment. FDA granted the application priority review. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
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