379 patients (99.2%) had at least one adverse event. 100% in the venetoclax-rituximab group and 98.4% in the bendamustine-rituximab group. Grade 3 or 4 adverse events were reported in 82% of the venetoclax-rituximab group and 70.2% of the bendamustine-rituximab group. The most common grade 3 or 4 adverse event was neutropenia with higher incidence in the venetoclax-rituximab group than in bendamustine-rituximab group (57.7% vs 38.8%), however the incident of grade 3 or 4 febrile neutropenia and infections were lower in the venetoclax-rituximab group. Grade 3 or 4 tumour lysis syndrome was reported in 6 (3.1%) in the venetoclax-rituximab group and in 2 patients (1.1%) in the bendamustine-rituximab group.
© NEJM 2018
Richter’s transformation was confirmed in 6 patients in the venetoclax-rituximab group and in 5 patients in the bendamustine-rituximab group.
Death occurred in 10 (5.2%) patients in the venetoclax-rituximab group and in 11 (5.9% in the bendamustine-rituximab group (4 fatal infections in each group).
48 discontinued venetoclax and 13 discontinued rituximab in the venetoclax-rituximab arm while 27 discontinued bendamustine-rituximab.
Follow up data from subsequent publication from Kater et al showed that 130 of the 194 patients randomised to venetoclax-rituximab arm (67%) completed two years of planned venetoclax. 11% had progressive disease, 1% died without progressive disease, 15% withdrew due to adverse events and 6% for other reasons.r
Adverse events (AEs) that lead to withdrawal during combination therapy were neutropenia (2.1%), thrombocytopenia (1.5%), neoplasm (1%), febrile neutropenia, anaemia, autoimmune haemolytic anaemia, acute respiratory failure, appendicitis, peritoneal tuberculosis, pneumonia, pyrexia, status epilepticus and sudden cardiac death, all accounting for 0.5% each. AEs leading to withdrawal during single agent therapy were neoplasms (2.6%), neutropenia (1.5%), thrombocytopenia (1%); whilst ALT increase, ascites, asthenia, autoimmune haemolytic anaemia, Crohn’s disease, diarrhoea, immune thrombocytopenic purpura, hydrothorax, pneumonia, sudden death and vertigo all accounting for 0.5% each.r