FDA approval of subcutaneous daratumumab, carfilzomib, and dexamethasone for R/R MM

On November 30, 2021, it was announced that the U.S. Food and Drug Administration (FDA) approved the use of subcutaneous daratumumab (daratumumab + hyaluronidase-fihj) in combination with carfilzomib and dexamethasone (Dara-Kd) for the treatment of adult patients with relapsed/refractory multiple myeloma (R/R MM) with ≤3 prior lines of therapy. The decision was based on results of a single cohort of patients in the ongoing PLEIADES trial (NCT03412565).¹

PLEIADES trial^1,2

• A phase II, multicenter, multicohort study investigating the use of subcutaneous daratumumab in combination with standard MM treatment regimens
• Trial start date: April 26, 2018
• Primary completion date: August 12, 2020
• Estimated end date: June 7, 2022
• Enrollment in Dara-Kd cohort: adult patients with R/R MM with ≤3 prior lines of therapy (n = 66)
• Primary outcome measure: overall response rate defined as the percentage of patients who achieve partial response or better based on the International Myeloma Working Group criteria

Results¹

• Overall response rate: 84.8% (95% confidence interval, 73.9–92.5%)
• With a median follow-up of 9.2 months, the median duration of response had not yet been reached
  • Approximately 85.2% of patients maintained a response for ≥6 months
  • 82.5% of patients maintained a response for ≥9 months
• The most common adverse reactions occurring in ≥20% of patients were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and peripheral edema

Recommended dosing regimen¹

Subcutaneous daratumumab (1,800 mg/30,000 units daratumumab/hyaluronidase) and dexamethasone are administered as per standard dosing.

The recommended dosing of carfilzomib intravenously over 30 minutes in each 28-day cycle is:

• Once weekly:
  • 20 mg/m² on Cycle 1 Day 1, and if tolerated 70 mg/m² on Days 8 and 15
  • Then 70 mg/m² on Days 1, 8, and 15 for Cycle 2 onwards
• Or twice weekly:
  • 20 mg/m² on Cycle 1 Days 1 and 2, and if tolerated 56 mg/m² on Days 8, 9, 15, and 16
  • Then 56 mg/m² on Days 1, 2, 8, 9, 15, and 16 for Cycle 2 onwards