Intravenous daratumumab for treatment of patients with multiple myeloma involves a lengthy infusion that affects quality of life, and infusion-related reactions are common. Subcutaneous daratumumab is thought to be easier to administer and to cause fewer administration-related reactions. In the new COLUMBA study, scientists from the USA tested the non-inferiority of subcutaneous daratumumab to intravenous daratumumab.
In this ongoing, multicentre (147 sites in 18 countries), open-label, randomised, phase 3 trial, adult patients were recruited if they had confirmed relapsed or refractory multiple myeloma. Patients had received at least three previous therapies, including a proteasome inhibitor and immunomodulatory drug, or were double refractory to both a proteasome inhibitor and immunomodulatory drug.
Patients were randomly assigned to receive daratumumab either subcutaneously (subcutaneous group) or intravenously (intravenous group). Randomisation was stratified on the basis of baseline bodyweight (≤65 kg, 66–85 kg, >85 kg), previous therapy lines (≤four vs >four), and myeloma type (IgG vs non-IgG).
Patients received 1800 mg of subcutaneous daratumumab or intravenous daratumumab once weekly (cycles 1–2), every 2 weeks (cycles 3–6), and every 4 weeks thereafter (28-day cycles) until progressive disease or toxicity. Primary endpoints were overall response and maximum Ctrough concentration.
In total, 655 patients were screened, of whom 522 were recruited and randomly assigned (subcutaneous group n=263; intravenous group n=259). Three patients in the subcutaneous group and one in the intravenous group did not receive treatment and were not evaluable for safety. At a median follow-up of 7·5 months (IQR 6·5–9·3), overall response was seen in 108 (41%) of 263 patients in the subcutaneous group and 96 (37%) of 259 in the intravenous group (relative risk 1·11, 95% CI 0·89–1·37). The maximum C trough was 593 μg/mL (SD 306) in the subcutaneous group and 522 μg/mL (226) in the intravenous group.
The most common grade 3 and 4 adverse events were anaemia, that affected 34 (13%) of 260 patients in the subcutaneous group and 36 (14%) of 258 patients in the intravenous group. Also neutropenia (34/13% and 20/8%), and thrombocytopenia (36/14% and 35/14%). Pneumonia was the only serious adverse event in more than 2% of patients (7/3% in the subcutaneous group and 11/4% in the intravenous group). There was one death resulting from a treatment-related adverse event in the subcutaneous group and four in the intravenous group.
It was found that subcutaneous daratumumab was not inferior to intravenous daratumumab in terms of efficacy and pharmacokinetics. However, subcutaneous administration does present an improved safety profile in patients with relapsed or refractory multiple myeloma. These data could contribute to the approval of the subcutaneous daratumumab formulation by regulatory bodies.