On November 30, 2021, daratumumab/hyaluronidase-fihj and carfilzomib were approved for use in combination with dexamethasone for adults with relapsed or refractory multiple myeloma who had one to three prior lines of therapy.1,2
Supporting Efficacy Data
Approval was based on findings in a cohort of the PLEIADES trial (ClinicalTrials.gov identifier NCT03412565), in which 66 patients with at least one prior line of therapy received the combination product containing daratumumab at 1,800 mg and hyaluronidase-fihj at 30,000 units plus carfilzomib in a 20/70 mg/m2 once-weekly regimen and dexamethasone.
Partial response or better was achieved in 56 patients (84.8%, 95% confidence interval = 73.9%–92.5%). At a median follow-up of 9.2 months, the median duration of response was not reached, with responses maintained at ≥ 6 and ≥ 9 months in 85.2% and 82.5% of patients.
How It Is Used
The recommended dose of the combination is daratumumab at 1,800 mg and hyaluronidase-fihj at 30,000 units given subcutaneously once weekly in weeks 1 through 8, once every 2 weeks in weeks 9 through 24, and once every 4 weeks starting at week 25 until disease progression or unacceptable toxicity.
The recommended dosage regimens of carfilzomib via intravenous infusion are 20 mg/m2 on cycle 1/day 1; 70 mg/m2 on cycle 1, days 8 and 15; and then days 1, 8, and 15 of each 28-day cycle; or 20 mg/m2 on cycle 1/days 1 and 2; 56 mg/m2 on cycle 1/days 8, 9, 15, and 16; and then days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.
In the PLEIADES trial, the most common adverse events of any grade (≥ 20%) were upper respiratory tract infection (52%), fatigue (39%), insomnia (33%), hypertension (32%), diarrhea (29%), cough (24%), dyspnea (23%), headache (23%), pyrexia (21%), nausea (21%), and peripheral edema (20%). The most common grade 3 or 4 adverse events included hypertension (21%) and insomnia (6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (50%) and decreased platelets and leukocytes (18% each). Serious adverse events occurred in 27% of patients. Adverse events led to discontinuation of treatment in 6%. Fatal adverse events occurred in 3%.
Daratumumab/hyaluronidase-fihj has warnings/precautions for hypersensitivity and other administration reactions, cardiac toxicity in patients with light chain amyloidosis, neutropenia, thrombocytopenia, embryofetal toxicity, and interference with cross-matching and red blood cell antibody screening. It is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any formulation components.
Carfilzomib has warnings/precautions for cardiac toxicities, acute renal failure, tumor-lysis syndrome, pulmonary toxicity, pulmonary hypertension, dyspnea, hypertension, venous thrombosis, infusion-related reactions, hemorrhage, thrombocytopenia, hepatic toxicity, thrombotic microangiopathy, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy, increased fatal and serious toxicities in combination with melphalan and prednisone in newly diagnosed transplant-ineligible patients, and embryofetal toxicity.
1. Darzalex faspro (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use, prescribing information, Janssen Biotech, November 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf. Accessed December 10, 2021.
2. Kyprolis (carfilzomib) for injection, for intravenous use, prescribing information, Amgen, November 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202714s033lbl.pdf. Accessed December 10, 2021.