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Shaji K. Kumar, MD
Shaji K. Kumar, MD
Posted: Friday, January 30, 2026
On January 27, the U.S. Food and Drug Administration (FDA) approved the CD38-directed monoclonal antibody daratumumab plus hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
CEPHEUS
Efficacy was evaluated in CEPHEUS (ClinicalTrials.gov identifier NCT03652064), an open-label, randomized, active-controlled trial in patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant or refused it as initial therapy. The effectiveness of daratumumab and hyaluronidase plus VRd had not been established in patients who refused autologous stem cell transplant as initial therapy.
A total of 395 patients were randomly assigned: 197 to the daratumumab and hyaluronidase plus VRd arm and 198 to the VRd arm. The major efficacy outcome measures were overall measurable residual disease (MRD) negativity rate and progression-free survival by independent review committee based on International Myeloma Working Group response criteria. The MRD negativity rate was 52.3% in the daratumumab and hyaluronidase plus VRd arm and 34.8% in the VRd arm (P = .0005). The progression-free survival hazard ratio was 0.60 (95% confidence interval = 0.41–0.88; P = .0078).
The prescribing information includes warnings and precautions for hypersensitivity and other administration 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 amyloidosis.
Recommended Dosage
The recommended dose is 1,800 mg of daratumumab and 30,000 units of hyaluronidase.
Regulatory Review Process
This review used the Assessment Aid, a voluntary applicant submission designed to facilitate the FDA’s assessment.
U.S. Food and Drug Administration
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