The FDA has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The decision, dated January 27, 2026, adds a subcutaneous anti-CD38–based quadruplet option in the frontline setting for patients who cannot proceed to transplant.
The approval is supported by the phase 3 CEPHEUS trial (NCT03652064), an open-label, randomized, active-controlled study in patients with newly diagnosed multiple myeloma who were ineligible for transplant or refused transplant as initial therapy. The FDA noted that the effectiveness of the Darzalex Faspro–VRd regimen has not been established in patients who refused autologous stem cell transplant as initial therapy. A total of 395 patients were randomized to receive Darzalex Faspro plus VRd (n=197) or VRd alone (n=198).
Key efficacy endpoints were overall minimal residual disease (MRD) negativity rate and progression-free survival (PFS), both assessed by an independent review committee using International Myeloma Working Group response criteria. The MRD negativity rate reached 52.3% in the Darzalex Faspro–VRd arm compared with 34.8% in the VRd arm, corresponding to a p-value of 0.0005. The PFS hazard ratio was 0.60, with a 95% confidence interval of 0.41 to 0.88 and a p-value of 0.0078, indicating a reduction in the risk of disease progression or death for the combination regimen versus VRd alone.
The prescribing information for Darzalex Faspro carries Warnings and Precautions for hypersensitivity and other administration-related reactions, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, interference with cross-matching and red blood cell antibody screening, and cardiac toxicity in patients with light chain (AL) amyloidosis. The recommended dose of Darzalex Faspro in this regimen is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase), with dosing guidance for the backbone agents provided in their respective labels.
The FDA review utilized the Assessment Aid, a voluntary submission from the applicant designed to facilitate regulatory assessment. The agency reminded healthcare professionals to report serious adverse events associated with medicines and devices to the MedWatch Reporting System and noted that its Oncology Center of Excellence provides support for single-patient INDs for investigational oncology products through Project Facilitate.
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