Adverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202

Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however differences in treatment duration, 6 monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons. We introduce the AE burden score (AE(sc)) to compare AEs, calculated for each patient by summing over products of reporting period length and grade for each all-cause grade 1–4 AE and dividing by the length of time over which AEs are assessed. 176 patients received BR and 361 ibrutinib alone or with 6 cycles of rituximab. At 38 months median follow-up, 64% remained on ibrutinib. Median AE(sc) was higher with BR versus ibrutinib in the first 6 cycles (7.2 versus 4.9, p<0.0001). Within ibrutinib arms, median AE(sc) decreased significantly to 3.7 after 6 cycles (p<0.0001). 10% and 14% of BR and ibrutinib patients discontinued treatment for AEs. In ibrutinib arms, cumulative incidence of grade 3 or higher atrial fibrillation, hypertension, and infection (AEs of clinical interest) at 12 months was 4.5%, 17.5%, and 12.8%, respectively, and increased more slowly thereafter to 7.7%, 25.4%, and 20.5% at 36 months. Analytical tools including the AE(sc) and cumulative incidence of AEs can help to better characterize AE burden over time.