Open AccessAdverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202
Author(s) -
Amy S. Ruppert,
Allison M Booth,
Wei Ding,
Nancy L. Bartlett,
Danielle M. Brander,
Steven Coutre,
Jennifer R. Brown,
Sreenivasa Nattam,
Richard A. Larson,
Harry P. Erba,
Mark R. Litzow,
Carolyn Owen,
Charles Kuzma,
Jeremy S. Abramson,
Richard F. Little,
Scott E. Smith,
Richard Stone,
John C. Byrd,
Sumithra J. Mandrekar,
Jennifer A. Woyach
Publication year - 2021
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/s41375-021-01342-x
Subject(s) - ibrutinib , bendamustine , medicine , adverse effect , rituximab , cumulative incidence , gastroenterology , chronic lymphocytic leukemia , lymphoma , leukemia , cohort
Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six 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. A total of 176 patients received BR and 361 ibrutinib alone or with six 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 six cycles (7.2 versus 4.9, p < 0.0001). Within ibrutinib arms, median AE sc decreased significantly to 3.7 after six 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. ClinicalTrials.gov identifier: NCT01886872.