Data could contribute to the approval of the SC daratumumab formulation by regulatory bodies — researchers
Subcutaneous (SC) daratumumab was non-inferior to intravenous (IV) daratumumab in terms of efficacy and pharmacokinetics and had an improved safety profile in patients with relapsed or refractory multiple myeloma (R/RMM), a study is reporting.
Researchers from the COLUMBA trial also said the data could contribute to the approval of the SC daratumumab formulation by regulatory bodies.
IV daratumumab for treatment of patients with multiple myeloma (MM) involved a lengthy infusion that affected quality of life, and infusion-related reactions were common, Mateos et al noted in the May 2020 edition of the Lancet Haematology journal.
SC daratumumab, they added, was also thought to be easier to administer and to cause fewer administration-
related reactions.
For their ongoing, multicentre phase III trial, they tested the non-inferiority of SC daratumumab to IV daratumumab.
Patients across 147 sites in 18 countries were randomly assigned (1:1) by a computer-generated randomisation schedule and balanced using randomly permuted blocks to receive daratumumab subcutaneously (SC group) or intravenously (IV group).
Patients received 1,800 mg of SC daratumumab co-formulated with 2,000 U/mL recombinant human hyaluronidase PH20 or 16 mg/kg of IV daratumumab once weekly (cycles 1-2), every two weeks (cycles 3-6), and every four weeks thereafter (28-day cycles) until progressive disease or toxicity.
The co-primary endpoints were overall response and maximum trough concentration (Ctrough; cycle 3, day 1 pre-dose).
Between October 31, 2017, and December 27, 2018, some 655 patients were screened, of whom 522 were recruited and randomly assigned (SC group n=263; IV group n=259). Three patients in the SC group and one in the IV group did not receive treatment and were unevaluable for safety.
An overall response was seen in 108 (41%) of 263 patients in the SC group and 96 (37%) of 259 in the IV group, while the geometric means ratio for Ctrough was 107.93 per cent, and the maximum Ctrough was 593 μg/mL (SD 306) in the SC group and 522 μg/mL (226) in the IV group. The results also showed that the most common grade 3 and 4 adverse events were anaemia (34 [13%] of 260 patients evaluable for safety in the SC group and 36 [14%] of 258 patients in the IV group), neutropenia (34 [13%] and 20 [8%]), and thrombocytopenia (36 [14%] and 35 [14%]).
Pneumonia was the only serious adverse event in more than 2 per cent of patients (seven [3%] in the SC group and 11 [4%] in the IV group). There was one death resulting from a treatment-related adverse event in the SC group (febrile neutropenia) and four in the IV group (sepsis [n=2], hepatitis B reactivation [n=1], and Pneumocystis jirovecii pneumonia [n=1]).
Lancet Haematology, published online, doi: 10.1016/