On November 30, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with carfilzomib (Kyprolis) plus dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
PLEIADES Trial
Efficacy was evaluated in a single-arm cohort of PLEIADES (ClinicalTrials.gov identifier NCT03412565), a multicohort, open-label trial. This cohort enrolled 66 patients with relapsed or refractory multiple myeloma who had received at least one prior line of therapy. Patients received daratumumab and hyaluronidase-fihj at 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, which was 84.8% (95% confidence interval [CI] = 73.9%–92.5%). At a median follow-up of 9.2 months, the median duration of response had not been reached. An estimated 85.2% (95% CI = 72.5%–92.3%) of patients maintained a response for at least 6 months, and 82.5% (95% CI = 68.9%–90.6%) maintained a response for at least 9 months.
The most common adverse reactions (≥ 20%) occurring in patients treated with the triplet were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema.
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 to 8, once every 2 weeks from weeks 9 to 24, and once every 4 weeks starting at week 25 until disease progression or unacceptable toxicity.
The recommended dosage regimens of carfilzomib when administered in combination with daratumumab and hyaluronidase-fihj are:
- Once-weekly 20/70 mg/m2 regimen: Carfilzomib at 20 mg/m2 administered by intravenous (IV) infusion over 30 minutes on cycle 1 day 1; 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 at 20 mg/m2 administered by IV infusion over 30 minutes on cycle 1 day 1 and day 2; 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, and 16 of each 28-day cycle.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
