FDA Approves Daratumumab Plus Hyaluronidase-Fihj, Carfilzomib, and Dexamethasone for Multiple Myeloma

Multiple myeloma.

The FDA has approved daratumumab plus hyaluronidase-fihj (Darlazex Faspro®, Janssen Biotech) in combination with carfilzomib (Kyprolis®, Amgen) plus dexamethasone for patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy.

“Daratumumab is a human immunoglobulin G kappa monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action,” wrote Ajai Chari, MD, Professor of Medicine, Hematology, and Medical Oncology at Mount Sinai, and colleagues in their publication of the PLEIADES trial (NCT03412565), in which the daratumumab plus hyaluronidase-fihj was tested in combination with standard treatment regimens. “To reduce patient and provider burden without compromising safety or efficacy, a subcutaneous co-formulation of daratumumab with recombinant human hyaluronidase in a total volume of 15 ml was developed.”

The multicenter, multicohort, open-label, phase 2 clinical trial upon which the approval was based enrolled 66 patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy. Patients received 1,800 mg daratumumab and 30,000 units hyaluronidase-fihj, administered subcutaneously in combination with 20/70 mg/m2 carfilzomib and dexamethasone. The primary end point was overall response rate.

At a median follow up of 9.2 months, the median duration of response had not been reached; an estimated 85.2% of patients maintained their response for at least 6 months, and 82.5% of patients maintained their response for at least 9 months.

The most common adverse reactions occurring in at least 20% of patients receiving daratumumab plus hyaluronidase-fihj, carfilzomib, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema.

“The primary analysis of the subcutaneous daratumumab plus carfilzomib/dexamethasone cohort demonstrated comparable clinical activity and safety to intravenous daratumumab plus carfilzomib/dexamethasone,” concluded Philippe Moreau, MD, Head of the Hematology Department at the University Hospital of Nantes, France, and colleagues in their published abstract at the 62nd ASH Annual Meeting and Exposition of the PLEIADES trial (NCT03412565), on which the approval was based.

The recommended dose of daratumumab plus hyaluronidase-fihj is 1,800 mg/30,000 units administered subcutaneously once weekly for Weeks 1 through 8, once every two weeks for Weeks 9 through 24, and once every four weeks beginning at Week 25, until disease progression or unacceptable toxicity. The recommended dose of carfilzomib is either a once-weekly 20/70 mg/m2 regimen (carfilzomib 20 mg/m2 administered via intravenous infusion over 30 minutes on Cycle 1 Day 1, followed by 70 mg/m2 as a 30-minute intravenous infusion on Day 8 and Day 15 if tolerated, and then on Day 1, 8, and 15 of each 28-day cycle) or in a twice-weekly 20/56 mg/m2 regimen (carfilzomib 20 mg/m2 administered by intravenous infusion over 30 minutes on Cycle 1 Days 1 and 2, followed by 56 mg/m2 administered by intravenous infusion over 30 minutes on Cycle 1 Days 8, 9, 15, and 16, and then Day 1, 2, 8, 9, 15, and 16 of each 28-day cycle).

For More Information

Chari A, Rodriguez-Otero P, McCarthy H, et al (2021). Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol, 192(5):869-878. DOI:10.1111/bjh.16980

Moreau P, Chari A, Haenel M, et al (2020). Subcutaneous daratumumab (DARA SC) plus standard-of-care (SoC) regimens in multiple myeloma (MM) across lines of therapy in the phase 2 Pleiades study: initial results of the Dara SC plus carfilzomib/dexamethasone (D-Kd) cohort, and updated results for the Dara SC plus bortezomib/melphalan/prednisone (D-VMP) and Dara SC plus lenalidomide/dexamethasone (D-Rd) cohorts. 62nd American Society of Hematology Annual Meeting & Exposition. Abstract 1380.

Clinicaltrials.gov (2021). A study to evaluate subcutaneous daratumumab in combination with standard multiple myeloma treatment regimens. NLM identifier: NCT03412565.

Darzalex Faspro® (daratumumab and hyaluronidase-fihj) prescribing information (2021). Janssen Biotech. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Kyprolis® (carfilzomib) prescribing information (2021). Amgen. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202714s033lbl.pdf

US Food & Drug Administration (2021). FDA approves Darzalex Faspro, Kyprolis, and dexamethasone for multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darzalex-faspro-kyprolis-and-dexamethasone-multiple-myeloma

Image credit: Dr Osaro Erhabor. Licensed under CC BY-SA 3.0

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