FDA approves Darzalex Faspro, Kyprolis, and Dexamethasone for Multiple Myeloma
On November 30, 2021, the Food and Drug Administration approved daratumumab + hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) and carfilzomib (Kyprolis, Amgen, Inc.) plus dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.
Efficacy was evaluated in a single-arm cohort of PLEIADES (NCT03412565), a multi-cohort, open-label trial. This cohort enrolled 66 patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy. Patients received Darzalex Faspro 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously in combination with Kyprolis (20/70 mg/m2 once weekly regimen) and dexamethasone.
The main efficacy outcome measure was overall response rate (ORR). 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.
The most common adverse reactions (≥20%) occurring in patients treated with Darzalex Faspro, Kyprolis, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.
The recommended Darzalex Faspro dose is 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 Week 25 until disease progression or unacceptable toxicity.
The recommended dosage regimens of Kyprolis when administered in combination with Darzalex Faspro are the following:
- Once weekly 20/70 mg/m2 regimen: Kyprolis 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: Kyprolis 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
View full prescribing information for Darzalex Faspro.
View full prescribing information for Kyprolis.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
