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FDA Approves Daratumumab and Hyaluronidase-fihj in Multiple Myeloma


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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:

  • In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
  • In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
  • In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
  • As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

COLUMBA Trial

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%).

PLEIADES Trial

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.


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