On July 30, 2024, the Food and Drug Administration approved daratumumab and hyaluronidase-fihj 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 transplant (ASCT).

Full prescribing information for daratumumab and hyaluronidase-fihj will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in PERSEUS (NCT03710603), an open-label, randomized, active-controlled trial in patients with newly diagnosed multiple myeloma eligible for ASCT. Enrollment was limited to patients 70 years of age and younger. A total of 709 patients were randomized: 355 to the hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone (hyaluronidase-fihj-VRd) arm and 354 to the bortezomib, lenalidomide, and dexamethasone (VRd) arm.

The major efficacy outcome measure was progression-free survival (PFS) as assessed by an independent review committee based on International Myeloma Working Group (IMWG) response criteria. PERSEUS demonstrated an improvement in PFS in the hyaluronidase-fihj-VRd arm as compared to the VRd arm; the median PFS had not been reached in either arm. Treatment with 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-value < 0.0001).

The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, oedema, pyrexia, upper respiratory infection, constipation, diarrhoea, musculoskeletal pain, insomnia, and rash.

The recommended hyaluronidase-fihj dose is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase). See the prescribing information for the dosage recommendations for the other drugs.

Source: FDA