On November 30, 2021, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro™), carfilzomib (Kyprolis®), and dexamethasone for adult patients with relapsed or refractory multiple myeloma who received one to three prior lines of therapy.
Efficacy was evaluated in a single-arm cohort, multicohort, open-label trial (PLEIADES; NCT03412565). The trial enrolled 66 patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy. Patients received daratumumab and hyaluronidase-fihj 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously in combination with carfilzomib (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 six months and 82.5% (95% CI = 68.9, 90.6) maintained response for at least nine months.
The most common adverse reactions occurring in 20% or more of patients treated with daratumumab and hyaluronidase-fihj, carfilzomib, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.
The recommended daratumumab and hyaluronidase-fihj dose is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously once weekly from weeks 1–8, once every two weeks from weeks 9–24, and once every four weeks starting at week 25 until patients experience disease progression or unacceptable toxicity.
The recommended dosage regimens of carfilzomib when administered in combination with daratumumab and hyaluronidase-fihj are the following:
- Once-weekly 20/70 mg/m2 regimen: carfilzomib 20 mg/m2 administered as a 30-minute IV infusion on cycle one, day 1; if a dose of 20 mg/m2 is tolerated, increase to 70 mg/m2 as a 30-minute IV infusion on cycle one, days 8 and 15, and maintain the dose for days 1, 8, and 15 of each 28-day cycle.
- Twice-weekly 20/56 mg/m2 regimen: carfilzomib 20 mg/m2 administered as a 30-minute IV infusion on cycle one, days 1 and 2; if a dose of 20 mg/m2 is tolerated, increase to 56 mg/m2 as a 30-minute IV infusion on cycle one, days 8, 9, 15, and 16, and maintain the dose for days 1, 2, 8, 9, 15, and 16 of each 28-day cycle
View the full prescribing information for daratumumab and hyaluronidase-fihj.
View the full prescribing information for carfilzomib.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application four months ahead of the goal date.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 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.