On November 30, 2021, the Food and Drug Administration approved daratumumab + hyaluronidase-fihj and carfilzomib 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 daratumumab + 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 the 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 daratumumab + hyaluronidase-fihj, carfilzomib, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhoea, cough, dyspnea, headache, pyrexia, nausea, and oedema peripheral.

The recommended daratumumab + 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 Week 25 until disease progression or unacceptable toxicity.

The recommended dosage regimens of carfilzomib, when administered in combination with daratumumab + hyaluronidase-fihj, are the following:

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.

View full prescribing information for daratumumab + hyaluronidase-fihj here.

View full prescribing information for carfilzomib here.

Source: FDA