The randomized, open-label, parallel assignment phase III COLUMBA (MMY3012) study (NCT03277105) investigated the impact of either subcutaneous (SC) or intravenous (IV) administration of daratumumab (Darzalex®) on response rates in patients with relapsed/refractory multiple myeloma (RRMM).
The study found that daratumumab, co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), administered subcutaneously is non-inferior to IV administration.
- Patients (N = 522) were randomized to either:
- SC daratumumab: 1800 mg with rHuPH20 2000 U/mL (N = 263)
- IV daratumumab: 16 mg/kg (N = 259)
- Both were administered:
- Once-weekly in cycles 1 and 2
- Every two weeks in cycles 3–6
- Every four weeks in cycle 7
- Continued until disease progression, unacceptable toxicity or study end
- Co-primary endpoints:
- Overall response rate (ORR)
- Maximum trough of daratumumab (Ctrough)
- Daratumumab serum pre-dose concentration on day 1 of cycle 3
- SC daratumumab: 41.1% (N = 263)
- IV daratumumab: 37.1% (N = 259)
- Mean Ctrough rate
- SC daratumumab: 499 mg/mL (N = 149)
- IV daratumumab: 463 mg/mL (N = 146)
No additional safety concerns were raised. The pharmaceutical company expected to present the data at an upcoming medical conference, publish in a peer-reviewed journal, and consider a regulatory submission for this formulation.
Providing daratumumab subcutaneously may result in a benefit to patients owing to the quicker and more convenient method of administration.