On July 9, 2021, daratumumab and hyaluronidase-fihj was approved for use in combination with pomalidomide and dexamethasone (Pd) for treatment of adults with multiple myeloma who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor.1
Supporting Efficacy Data
Approval was based on findings in the phase III APOLLO trial (ClinicalTrials.gov identifier NCT03180736). A total of 304 patients were randomly assigned to receive daratumumab/hyaluronidase with Pd (n = 151) or Pd alone (n = 153). Daratumumab/hyaluronidase was given at 1,800 mg of daratumumab/30,000 units of hyaluronidase subcutaneously (SC) once weekly from weeks 1 to 8, every 2 weeks from weeks 9 to 24, and every 4 weeks from week 25 until disease progression or unacceptable toxicity. Pomalidomide was given at 4 mg/d on days 1 to 21 of 28-day cycles, and dexamethasone was given at 40 mg/week (20 mg for patients aged > 75 years).
Median progression-free survival was 12.4 months in the daratumumab/hyaluronidase group vs 6.9 months in the control group (hazard ratio = 0.63, 95% confidence interval = 0.47–0.85, P = .0018). Partial response or better was observed in 68.9% vs 46.4% (P < .001).
How It Is Used
Daratumumab/hyaluronidase is for SC use only. The recommended dosage in the current indication is 1,800 mg of daratumumab/30,000 units of hyaluronidase given SC into the abdomen over approximately 3 to 5 minutes; it is given weekly during weeks 1 to 8, every 2 weeks during weeks 9 to 24, and every 4 weeks from week 25 until disease progression.
No dose reductions in daratumumab/hyaluronidase are recommended. Withholding treatment should be considered to allow recovery of blood cell counts in case of myelosuppression. Premedication and postmedication to prevent administration-related reactions and prophylaxis for herpes zoster reactivation are recommended.
In the APOLLO trial, the most common adverse events of any grade in the daratumumab/hyaluronidase plus Pd group were fatigue (46% vs 39% in Pd group alone), pneumonia (38% vs 27%), and upper respiratory infection (36% vs 22%). The most common grade 3 to 4 adverse events included pneumonia (23% vs 17%) and fatigue (13% vs 5%). The most common grade 3 or 4 hematologic toxicities were decreased neutrophils (84% vs 63%), decreased leukocytes (64% vs 40%), and decreased lymphocytes (59% vs 33%). Serious adverse events occurred in 50% of the daratumumab/hyaluronidase group, with the most common being pneumonia (15%). Treatment was discontinued due to adverse events in 2%. Fatal adverse events occurred in 7%.
Daratumumab/hyaluronidase has warnings/precautions for hypersensitivity and other administration reactions, cardiac toxicity in patients with light chain amyloidosis, neutropenia, thrombocytopenia, embryofetal toxicity, and interference with cross-matching and red blood cell antibody screening. Its use is contraindicated in patients with a history of severe hypersensitivity to daratumumab or any of the components of the formulation.
1. Darzalex Faspro (daratumumab and hyaluronidase-fihj) prescribing information, Janssen Biotech, Inc., July 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf. Accessed July 21, 2021.