EHA 2019: COLUMBA study

Article written by Maria Dalby. Interview by Hannah Chatfield.

Another study with significant practice implications is the COLUMBA study, presented by Professor Maria-Victoria Mateos (University Hospital of Salamanca, Spain). This study was designed to demonstrate that daratumumab administered by subcutaneous injection is as effective and safe as intravenous daratumumab in the RRMM setting. 

A total of 522 patients with double-refractory RRMM and at least three prior lines of therapy were included in the study and randomised 1:1 to receive daratumumab subcutaneously at a dose of 1,800mg or intravenously at a dose of 16mg/kg until disease progression.

The co-primary endpoints were non-inferiority of subcutaneous daratumumab versus intravenous daratumumab with respect to ORR and maximum trough concentration of daratumumab. At a median follow-up period of 7.46 months, 57% of patients in each treatment arm had discontinued study treatment, in most cases due to progressive disease. ORR in the subcutaneous daratumumab arm was 41.1% compared with 37.1% in the intravenous arm, and ≥VGPR and ≥CR rates were comparable in the two treatment arms. The ratio of maximum trough concentration of daratumumab on day 1 of cycle 3 was 107.93% for subcutaneous daratumumab versus intravenous daratumumab. Both co-primary endpoints met their respective criteria for non-inferiority. ORR was comparable across all pre-defined subgroups including body weight, and PFS and OS were comparable between the two treatment arms.

Patients in the subcutaneous daratumumab arm had significantly fewer infusion reactions compared with intravenous daratumumab (12.7% versus 34.5%; OR=0.28; 95% CI 0.18, 0.44; p<0.0001), with few grade 3 reactions and no grade 4 reactions. Apart from fewer infusion reactions, the safety profiles were comparable in the two arms. Patients receiving subcutaneous daratumumab were significantly more satisfied with their treatment, as shown by higher scores on the Modified Cancer Treatment Satisfaction Questionnaire, and the investigators concluded that the COLUMBA study results support the use of daratumumab at a uniform dose administered subcutaneously.