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

Abstract

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.

• Authors: 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 Erba, Mark Litzow, Carolyn Owen, Charles S Kuzma, Jeremy S Abramson, Richard F Little, Scott E Smith, Richard M Stone, John C Byrd, Sumithra J Mandrekar, Jennifer A Woyach
• Journal: Leukemia (Leukemia) Vol. 35 Issue 10 Pg. 2854-2861 (10 2021) ISSN: 1476-5551 [Electronic] England
• PMID: 34274940 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Piperidines
• ibrutinib
• Rituximab
• Bendamustine Hydrochloride
• Adenine

Topics

• Adenine (administration & dosage, analogs & derivatives)
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Atrial Fibrillation (chemically induced, epidemiology, pathology)
• Bendamustine Hydrochloride (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Hypertension (chemically induced, epidemiology, pathology)
• Infections (chemically induced, epidemiology, pathology)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, pathology)
• Male
• Piperidines (administration & dosage)
• Prognosis
• Rituximab (administration & dosage)
• Survival Rate