Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma

Abstract

In the primary analysis of the phase 3 COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581(315) μg/mL for DARA SC and 496(231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs 34.5%, respectively) and shorter administration time (3-5 minutes vs 3-7 hours) supporting DARA SC as a preferable therapeutic choice. ClinicalTrials.gov Identifier: NCT03277105.

Improved efficiency of daratumumab treatment of multiple myeloma adopting the subcutaneous route: A micro‐costing analysis in three Italian hematology centers

“…4 While in IV formulation dosing has to be adjusted according to patients' weight, SC daratumumab is administered as a flat dose, thus simplifying also drug preparation. 21 COLUMBA trial was a multicenter, open-label, randomized, Phase 3 study that proved the non-inferiority of SC daratumumab versus IV daratumumab in terms of efficacy, pharmacokinetics (maximum C trough , that is strongly correlated with efficacy, 3 ) and safety both in the first analysis, at 7.5 months of follow-up, 4 and in the final analysis at 29.3 months of follow-up. 3 The present study found that, by administering daratumumab subcutaneously instead of intravenously, it was possible to spare 78%, 59%, 80% of patient time, HCP active working time, and infusion chair time, respectively.…”

Monoclonal Antibodies: The Greatest Resource to Treat Multiple Myeloma

“…The overall response rate (ORR) and the maximal C trough on cycle 3 day 1 predose were the co-primary end goals in this study. For the two end goals, daratumumab and hyaluronidase-fihj were comparable to daratumumab IV [ 29 ].…”

Clinical Administration Characteristics of Subcutaneous and Intravenous Administration of Daratumumab in Patients With Multiple Myeloma at Mayo Clinic Infusion Centers

“…DARA SC and DARA IV are comparable with regards to efficacy, overall safety, and pharmacokinetics. 12,13 Additionally, DARA SC is associated with fewer ARRs compared with DARA IV, 12,13 and has other notable benefits of administration, including reduced administration time (3-5 minutes for DARA SC v 3-7 hours for DARA IV) and improved patient satisfaction. 8,9,12,14 With the increased use of DARA SC, there is a need to better characterize and assess the potential advantages of this formulation's use in real-world clinical practice.…”