Darzalex Faspro, Kyprolis and dexamethasone "three swords combined" to treat multiple myeloma

On November 30, 2021, the U.S. Food and Drug Administration approved Darzalex Faspro and KyPROLIS plus dexamethasone to treat patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior treatments.

Darzalex Faspro is a subcutaneous injection (SC) preparation of the CD38 monoclonal antibody drug daratumumab (Darzalex, Zhaoke®). Darzalex is the world's first CD38-mediated, cytolytic antibody drug and the first monoclonal antibody drug approved by the US FDA for the treatment of multiple myeloma (MM). The intravenous preparation of Darzalex was launched in 2015 and has become the backbone therapy for clinical treatment of multiple myeloma (MM) and is widely used in clinical first-line, second-line and multi-line treatments.

The efficacy of this therapy was evaluated in the single-arm cohort PLEIADES (NCT03412565), a multi-cohort, open-label trial. The cohort included 66 patients with relapsed or refractory multiple myeloma who had received at least one prior therapy. Patient receives subcutaneous injection of Darzalex Faspro 1800 mg/30,000 units [1,800 mg daratumumab and 30,000 units hyaluronidase] combined with Kyprolis (20/70 mg/m once weekly) and dexamethasone.

The main efficacy indicator is the overall effective 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 was not reached, with an estimated 85.2% (95% CI: 72.5, 92.3) maintaining a response for at least 6 months and 82.5% (95% CI: 68.9, 90.6) maintaining a 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 infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema.

The recommended dose of Darzalex Faspro is 1800 mg/30000 units [1800 mg daratumumab and 30,000 units of hyaluronidase], subcutaneously once a week from weeks 1 to 8, every 2 weeks from weeks 9 to 24, and every 4 weeks starting from week 25 until disease progression or unacceptable toxicity.