Toxicity
Adverse events (AEs) were common in both the GLOW and CAPTIVATE studies for patients on ibrutinib-venetoclax. The most common AE of any grade was diarrhoea (50.9% of patients in the GLOW study, 62% of patients in the CAPTIVATE study) and neutropenia (41.5% of patients in the GLOW study, 42% of patients in the CAPTIVATE study).rr In the GLOW study, grade 3 or greater AEs occurred in 75.5% of patients on the ibrutinib-venetoclax arm (compared to 69.5% of patients on the control arm). A breakdown of the most common grade 3 or greater AEs from the GLOW study is provided in Figure 3.
Figure 3. Grade 3 or greater AEs occurring in greater than 5% of patients in either arm of the GLOW study
© NEJM Evid 2022
Noting the younger patient population, fewer patients in the CAPTIVATE study developed atrial fibrillation (4%) compared to the GLOW study.
Tumour lysis syndrome (TLS) was uncommon, with no patients reported to have demonstrated TLS in either the GLOW or CAPTIVATE study. The ibrutinib lead in resulted in effective debulking in both studies, with the number of patients deemed high risk of TLS reducing from 24.5% to 1.9% (in the GLOW study) and 21% to 1% (in the CAPTIVATE study).
In the 4-year follow-up of the GLOW study, there were 15 deaths in the ibrutinib-venetoclax arm, 4 due to infection (2 COVID-19 related), 2 due to cardiac causes, 2 due to ischaemic stroke, 1 due to secondary malignancy, 1 due to progressive disease and 4 being unknown.r Secondary malignancy was seen in 10.4% of patients (compared to 13.3% in the control arm). Richter’s transformation was seen in 2.8% of patients (compared to 1.9% in the control arm).