Subcutaneous Versus Intravenous Daratumumab in Resistant Multiple Myeloma
Posted: Monday, May 4, 2020
Subcutaneous daratumumab was found to be noninferior to intravenous daratumumab in relation to both efficacy and pharmacokinetics in patients with relapsed or refractory multiple myeloma. Subcutaneous administration was also associated with fewer side effects, according to Saad Z. Usmani, MD, of the Levine Cancer Institute–Atrium Health, Charlotte, North Carolina, and colleagues. These results were published in The Lancet Haematology.
The noninferiority phase III COLUMBA trial recruited 522 patients with relapsed or refractory multiple myeloma from 147 sites in 18 countries. Patients had received at least three previous lines of therapy and had an Eastern Cooperative Oncology Group performance status score of up to 2. Patients were randomly assigned 1:1 to receive daratumumab intravenously (16 mg/kg) or subcutaneously (1,800 mg with 2,000 U/mL of recombinant human hyaluronidase PH20).
After a median follow-up of 7.5 months, the overall response and trough concentration met the predefined noninferiority criteria. A response was seen in 41% of the 263 patients in the subcutaneous group and in 37% of the 259 patients in the intravenous group (relative risk = 1.11). The geometric means ratio for trough concentration was 107.93%, with a maximum trough concentration in the subcutaneous group of 593 mg/mL and 522 mg/mL in the intravenous group.
Common grade 3 and 4 adverse events in the subcutaneous and intravenous group were anemia (13% and 14%, respectively), neutropenia (13% and 8%), and thrombocytopenia (14% and 14%). The sole serious adverse event that occurred in more than 2% of patients was pneumonia, affecting 3% of patients in the subcutaneous group and 4% in the intravenous group. One death occurred as a result of febrile neutropenia in the subcutaneous group. In the intravenous group, four patients died (two of sepsis, one of hepatitis B reactivation, and one of Pneumocystis jirovecii pneumonia.
Disclosures: For full author disclosures, visit thelancet.com.