FDA Alert

FDA Approves Daratumumab and Hyaluronidase-Fihj Plus VRd For Transplant-Ineligible Newly Diagnosed Multiple Myeloma

Edited by:
Anthony Calabro, MA

Key Highlights

  • The FDA approved daratumumab and hyaluronidase-fihj in combination with bortezomib, lenalidomide, and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma.
  • The approval is supported by results from the phase 3 CEPHEUS trial.
  • Combination therapy demonstrated higher MRD negativity and improved progression-free survival versus VRd alone.

On January 27, 2026, the FDA approved daratumumab and hyaluronidase-fihj in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adults with newly diagnosed multiple myeloma who are ineligible for an autologous stem cell transplant. The approval applies to patients for whom a transplant is not planned as initial therapy. The approval was based on efficacy and safety findings from CEPHEUS, an open-label, randomized, active-controlled trial enrolling adults with newly diagnosed multiple myeloma who were ineligible or refused an autologous stem cell transplant.

A total of 395 patients were randomized to receive daratumumab and hyaluronidase-fihj plus VRd (n = 197) or VRd alone (n = 198). The coprimary efficacy endpoints were minimal residual disease (MRD) negativity and progression-free survival, assessed by an independent review committee using International Myeloma Working Group criteria. The MRD negativity rate was 52.3%, with daratumumab and hyaluronidase-fihj plus VRd compared with 34.8% with VRd alone (P = .0005). The progression-free survival hazard ratio was 0.60 (95% CI, 0.41–0.88; P = .0078).

The prescribing information includes 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 amyloidosis.

The recommended dose of daratumumab and hyaluronidase-fihj is 1,800 mg of daratumumab with 30,000 units of hyaluronidase, administered subcutaneously.

Reference
U.S. Food and Drug Administration. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. Published January 27, 2026. Accessed January 28, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-newly