Daratumumab and Hyaluronidase-fihj Approved for Newly Diagnosed Multiple Myeloma
Expert Perspectives
By Lyn Brook
Published
The FDA has granted approval to daratumumab and hyaluronidase-fihj (Darzalex Faspro®, Janssen Research & Development, LLC) plus bortezomib, lenalidomide, and dexamethasone (VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).
Why it matters: Rahul Banerjee, MD, FACP, the Editor-in-Chief of Oncology Data Advisor and Assistant Professor of Medicine at the Fred Hutchinson Cancer Center, welcomed this news, saying, “These drugs in myeloma are not new, and I’ve been using this exact Dara-VRd regimen for years in newly diagnosed patients based on the phase 2 GRIFFIN study. The phase 3 PERSEUS study, which was the basis of this FDA approval, showed similar excellent findings supporting the addition of daratumumab here.”
What they studied: Efficacy and safety were measured in the phase 3, open-label, active-controlled trial in which 709 patients ≤70 years of age with newly diagnosed multiple myeloma were randomized 1:1 to receive either daratumumab and hyaluronidase-fihj plus VRd or VRd alone.
The primary efficacy outcome measured was progression-free survival as assessed by an independent review committee based on International Myeloma Working Group (IMWG).
What they found: In the daratumumab and hyaluronidase-fihj plus VRd arm, an improved progression-free survival was demonstrated compared with those receiving VRd alone. Progression-free survival was not reached in either arm. In addition, the daratumumab and hyaluronidase-fihj plus VRd arm experienced a reduction in the risk of disease progression or death by 60% compared to VRd alone.
Adverse events: The most common adverse events experienced in ≥20% of patients receiving daratumumab and hyaluronidase-fihj were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
Conclusion: “I’m excited about this FDA approval mainly from the perspective of disparities,” concluded Dr. Banerjee. “Even though Dara-VRd has been shown to be cost-effective in myeloma and is obviously better for patient quality of life and durations of remission, insurance companies have historically tried to block its approval through any number of evolving arguments: first that GRIFFIN hadn’t been published, then that it was published but a phase 2 study, then that the FDA hadn’t approved this regimen despite it being in all of our guidelines, etc. I still occasionally meet patients for transplant consultations in 2024 where, unfortunately, their primary oncologist had not been able to get insurance approval for Dara-VRd despite trying. With this FDA approval, I think the final barrier has been removed. CD38-directed monoclonal antibodies like daratumumab are the standard of care for induction in patients with multiple myeloma diagnosed in the US.”
Instructions: The recommended dosage is 1,800 mg of daratumumab and 30,000 units of hyaluronidase. Please refer to the prescribing information for the dosage recommendations for VRd.