On May 1, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adult patients with newly diagnosed, relapsed, or refractory multiple myeloma. This new product allows for subcutaneous dosing of daratumumab.
Daratumumab and hyaluronidase-fihj is approved for the following indications that intravenous daratumumab had previously received:
Efficacy of daratumumab and hyaluronidase-fihji monotherapy was evaluated in COLUMBA, an open-label noninferiority trial that randomly assigned 263 patients to daratumumab and hyaluronidase-fihj and 259 to intravenous (IV) daratumumab. The trial’s co-primary endpoints were overall response rate and pharmacokinetic endpoint of the maximum Ctrough predose on day 1 of cycle 3.
Daratumumab and hyaluronidase-fihj was noninferior to IV daratumumab in evaluating these two endpoints.
The overall response rate was 41.1% in patients treated with daratumumab and hyaluronidase-fihj and 37.1% for IV daratumumab, with a risk ratio of 1.11 (95% confidence interval [CI] = 0.89–1.37). The geometric mean ratio comparing daratumumab and hyaluronidase-fihj to IV daratumumab for maximum Ctrough was 108% (90% CI = 96%–122%).
Efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib/melphalan/prednisone was evaluated in a single-arm cohort of PLEIADES, a multicohort, open‑label trial. Eligible patients were required to have newly diagnosed multiple myeloma and were ineligible for transplant. The major efficacy outcome measure, overall response rate, was 88.1% (95% CI = 77.8%–94.7%).
Efficacy of daratumumab and hyaluronidase-fihj in combination with lenalidomide/dexamethasone was evaluated in a single-arm cohort of this trial. Eligible patients had received at least one prior line of therapy. Overall response rate was 90.8% (95% CI = 81.0%–96.5%).
The most commonly reported adverse reaction (≥ 20%) with daratumumab and hyaluronidase-fihj monotherapy was upper respiratory tract infection. The most common adverse reactions (≥ 20%) with daratumumab and hyaluronidase-fihj plus bortezomib/melphalan/prednisone are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. The most common adverse reactions (≥ 20%) with daratumumab and hyaluronidase-fihj plus lenalidomide/dexamethasone are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.
The most common hematology laboratory abnormalities (≥ 40%) with daratumumab and hyaluronidase-fihj are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
The recommended dose of daratumumab and hyaluronidase-fihj is 1,800 mg of daratumumab and 30,000 units of hyaluronidase administered subcutaneously into the abdomen over approximately 3 to 5 minutes, according to the recommended schedule.