FDA Approves Subcutaneous Daratumumab Triplet for R/R Multiple Myeloma

The approval is based on the phase 2 PLEAIDES study, which found the agent had an ORR of 84.8%, with 82.5% of patients still responding after 9 months.

The FDA has granted approval to subcutenous daratumumab (Darzalex) plus hyaluronidase-fihj (Faspro) and carfilzomib (Kyprolis) plus dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, according to a press release by the FDA.1

The recommended dose of daratumumab plus hyaluronidase-fihj is 1,800 mg/30,000 units administered subcutaneously once weekly from weeks 1 to 8, once every 2 weeks from 9 to 24, and once every 4 weeks starting week 25 until disease progression or unacceptable toxicity.

The approval is based on the phase 2 PLEIADES study (NCT03412565), which has an actual enrollment of 265 participants and an estimated completion date of June 7, 2022. The primary end points of the study are overall response rate (ORR), and the rate of very good partial responses or better. Secondary end points include the maximum observed serum concentrations, percentage of participants with infusion-related reactions, duration of response, and the percentage of participants who are minimal residual disease negative.1,2

The arm of the study that looked at the newly approved combination enrolled 66 participants who relapsed or refractory multiple myeloma who received at least one prior line of therapy. The ORR was 84.8% (95% CI, 73.9%-92.5%). At the median follow-up of 9.2 months, the median duration of response had not been reached. An estimated 85.2% of patients maintained a response for at least 6 months (95% CI, 72.5%-92.3%) and 82.5% maintained a response for at least 9 months (95% CI, 68.9%-90.6%).1

In terms of safety, common adverse events include upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.


1. FDA approves Darzalex Faspro, Kyprolis, and Dexamethasone for multiple myeloma. News release. FDA. November 30, 2021. Accessed December 1, 2021. https://bit.ly/3o9U8GQ.

2. A study to evaluate subcutaneous daratumumab in combination with standard multiple myeloma treatment regimens. ClincialTrials.gov. Accessed December 1, 2021. https://bit.ly/3ro6RHW