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

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

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 (AEsc) 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 AEsc was higher with BR versus ibrutinib in the first six cycles (7.2 versus 4.9, p < 0.0001). Within ibrutinib arms, median AEsc 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 AEsc and cumulative incidence of AEs can help to better characterize AE burden over time. ClinicalTrials.gov identifier: NCT01886872.

Full Text

Duke Authors

Cited Authors

  • Ruppert, AS; Booth, AM; Ding, W; Bartlett, NL; Brander, DM; Coutre, S; Brown, JR; Nattam, S; Larson, RA; Erba, H; Litzow, M; Owen, C; Kuzma, CS; Abramson, JS; Little, RF; Smith, SE; Stone, RM; Byrd, JC; Mandrekar, SJ; Woyach, JA

Published Date

  • October 2021

Published In

Volume / Issue

  • 35 / 10

Start / End Page

  • 2854 - 2861

PubMed ID

  • 34274940

Pubmed Central ID

  • PMC8744070

Electronic International Standard Serial Number (EISSN)

  • 1476-5551

Digital Object Identifier (DOI)

  • 10.1038/s41375-021-01342-x

Language

  • eng

Conference Location

  • England