The FDA approved combination daratumumab + hyaluronidase-fihj (Darzalex Faspro), carfilzomib (Kyprolis), and dexamethasone to treat adult patients with relapsed or refractory multiple myeloma (RRMM) who progressed following treatment with one to three prior lines of therapy.
The treatment combination’s approval was based on findings from the single-arm, multi-cohort, open-label PLEIADES trial, which evaluated the treatment’s efficacy in a cohort of 66 patients with RRMM who had received at least one prior line of therapy. In the trial, patients received 1,800 mg daratumumab and 30,000 units hyaluronidase administered subcutaneously in combination with intravenous carfilzomib (20/70 mg/m2 once weekly regimen) and dexamethasone.
“The main efficacy outcome measure was overall response rate (ORR),” the FDA explained. “The ORR was 84.8% (95% CI: 73.9%, 92.5%). At a median follow-up of 9.2 months, the median duration of response had not been reached and an estimated 85.2% (95% CI: 72.5, 92.3) maintained response for at least 6 months and 82.5% (95% CI: 68.9, 90.6) maintained response for at least 9 months.”
Based on these findings, the recommended dose for daratumumab + hyaluronidase-fihj is 1,800 mg /30,000 units administered subcutaneously one weekly from weeks 1 to 8, once every two weeks from weeks 9 to 24, and once every four weeks from week 25 until disease progression or unacceptable toxicity.
As for carfilzomib, the FDA noted that the recommended dose when administered with daratumumab + hyaluronidase is:
- “Once weekly 20/70 mg/m2 regimen: [Carfilzomib] 20 mg/m2 administered by IV infusion over 30 minutes on Cycle 1 Day 1 and if a dose of 20 mg/m2 is tolerated, 70 mg/m2 as a 30-minute IV infusion on Cycle 1, Day 8 and Day 15, and then Day 1, 8, and 15 of each 28-day cycle.
- “Twice weekly 20/56 mg/m2 regimen: [Carfilzomib] 20 mg/m2 administered by IV infusion over 30 minutes on Cycle 1 Day 1 and Day 2 and, if a dose of 20 mg/m2 is tolerated, 56 mg/m2 administered by IV infusion over 30 minutes on Cycle 1, Day 8, 9, 15, and 16, and then on Day 1, 2, 8, 9, 15, 16 of each 28-day cycle.”
The most common adverse reactions associated with the treatment combination included upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema.
Daratumumab + hyaluronidase-fihj is manufactured by Janssen Biotech, Inc.; carfilzomib is manufactured by Amgen, Inc.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 468
Topic ID: 78,468,730,468,192,725,925
