On January 27, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. Daratumumab and hyaluronidase-fihj is given as a subcutaneous injection; daratumumab is a monoclonal antibody targeting CD38 and hyaluronidase-fihj is an absorption modifier that allows for faster injection.
Efficacy and Safety
Efficacy for the combination regimen was evaluation in the open-label, randomized, active-controlled CEPHEUS trial (ClinicalTrials.gov identifier NCT03652064) of patients with newly diagnosed multiple myeloma who were ineligible for or who refused autologous stem cell transplant as their initial therapy; however, the effectiveness of the regimen has not been established for patients who refused autologous stem cell transplant as their initial therapy.
In the study, a total of 395 patients were randomly assigned 1:1 to either the daratumumab and hyaluronidase-fihj with VRd arm (n = 197) and or the VRd-alone arm (n = 198). The major efficacy outcome measures were overall measurable residual disease negativity rate and progression-free survival as assessed by an independent review committee based on International Working Group response criteria.
The measurable residual disease negativity rate was 52.3% in the daratumumab and hyaluronidase-fihj with VRd arm and 34.8% in the VRd-alone arm (P = .0005). The hazard ratio for progression-free survival was 0.60 (95% confidence interval = 0.41–0.88; P = .0078).
Warnings and Dosage
The prescribing information for daratumumab and hyaluronidase-fihj 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.
The recommended dose for daratumumab and hyaluronidase-fihj is 1,800 mg of daratumumab and 30,000 units of hyaluronidase. See the prescribing information for the dosage recommendations for the other drugs in the combination regimen.
