Subcutaneous (SC) daratumumab was found to be noninferior to intravenous (IV) daratumumab for the treatment of relapsed or refractory (R/R) multiple myeloma (MM) in a recent study reported in The Lancet Haematology.
The multicenter, international phase 3 COLUMBA trial (ClinicalTrials.gov Identifier: NCT03277105) randomly assigned R/R MM to receive daratumumab by either SC (263 patients) or IV (259 patients) administration. Groups were stratified by bodyweight at baseline, receipt of more than 4 lines of prior therapy, and by whether the MM was associated with immunoglobulin G. Primary endpoints included the overall response rate (ORR) and the maximum trough concentration.
The median study follow-up occurred at 7.5 months, with a median of 6 cycles of therapy given to each group. For both primary endpoints, SC daratumumab demonstrated noninferiority. The ORRs were 41% for the SC group and 37% for the IV group. The mean maximum trough concentrations were 593 mg/mL for the SC group and 522 mg/mL for the IV group. The geometric means ratio of maximum trough concentration was 107.93% for SC compared with IV administration.
The median progression-free survival times were 5.6 months and 6.1 months for the SC group and IV group, respectively. Rates of progression or death were 51% for both groups at follow-up.
Safety analyses included 260 patients from the SC group and 258 patients from the IV group. Grade 3 or 4 anemia occurred in 13% of patients from the SC safety population and 14% of those in the IV safety population. Grade 3 or 4 thrombocytopenia was reported in 14% of patients in each group. Treatment-related fatalities were reported for 1 patient in the SC group and 4 in the IV group. Overall, grade 5 adverse events occurred in 5% of patients in the SC group and 7% of patients in the IV group.
The study investigators concluded that SC administration of daratumumab was noninferior to IV administration for this patient population in terms of both efficacy and pharmacokinetics. The investigators also noted that patient satisfaction appeared to be higher for patients receiving SC daratumumab.
Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial [published online March 23, 2020]. Lancet Haematol. doi: 10.1016/S2352-3026(20)30070-3