On July 9, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with pomalidomide and dexamethasone for adult patients with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.
Efficacy was evaluated in APOLLO (ClinicalTrials.gov identifier NCT03180736), an open-label, active-controlled trial. In the study, 304 patients were randomly assigned 1:1 to receive daratumumab and hyaluronidase-fihj with pomalidomide and dexamethasone (Pd) vs Pd alone.
Patients received daratumumab and hyaluronidase-fihj at 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously once weekly from weeks 1 to 8, once every 2 weeks from weeks 9 to 24 and once every 4 weeks starting with week 25 until disease progression or unacceptable toxicity, with pomalidomide at 4 mg once daily orally on days 1 to 21 of each 28-day cycle; and dexamethasone at 40 mg per week (or a reduced dose of 20 mg per week for patients aged > 75 years).
The main efficacy outcome measure was progression-free survival. The median progression-free survival was 12.4 months in the daratumumab and hyaluronidase-fihj plus Pd treatment group and 6.9 months in the Pd treatment group (hazard ratio = 0.63, 95% confidence interval = 0.47–0.85, P = .0018), representing a 37% reduction in the risk of disease progression or death for patients treated with daratumumab and hyaluronidase-fihj plus Pd vs Pd alone.
The most common adverse reactions (≥ 20%) in patients with multiple myeloma who received daratumumab and hyaluronidase-fihj plus Pd were fatigue, pneumonia, upper respiratory tract infection, and diarrhea.
The recommended dosage of daratumumab and hyaluronidase-fihj is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously into the abdomen over approximately 3 to 5 minutes according to the recommended schedule.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.