Population-level impact of ibrutinib for chronic lymphocytic leukemia in British Columbia, Canada

Abstract

Ibrutinib has dramatically changed the treatment landscape for chronic lymphocytic leukemia (CLL) since its availability in British Columbia (BC), Canada in 2014. We analyzed patterns of use and real-world survival outcomes in 370 patients who received ibrutinib for first-line (1 L, n = 35) and relapsed/refractory (R/R, n = 335) CLL between 2014–2018 in BC. Dose reductions and interruptions were frequent in 32% and 27%, respectively. With a median follow-up of 27.6 months, 35% of patients discontinued ibrutinib, primarily for adverse events (AEs) rather than progressive disease. Over the course of treatment, 87% of patients experienced at least one adverse event. The 2-year overall survival (OS) and event-free survival (EFS) were excellent at 83.9% and 76.1%, respectively, with medians not reached. However, patients who discontinued ibrutinib had a median OS of 32.5 months and median EFS of only 3.8 months from time of discontinuation, highlighting the need to minimize toxicity in the real-world.

Keywords:

• Chronic lymphocytic leukemia
• ibrutinib
• BTK inhibitor
• population-based
• real-world

Author contributions

R.S.K, C.L.T. and A.S.G. conceived the research. R.S.K. and S.J.H. collected the data. R.S.K. and A.S.G. completed the data cleaning, analyzed the data, performed the statistical analysis, and drafted the original manuscript. All remaining authors assisted in the data collection and revision of the manuscript.

Disclosure statement

K.J.S. has received research funding from Roche, honoraria from Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, Abbvie and serves on the Steering Committee for BeiGene. D.V. has received research funding from Roche and AstraZeneca and honoraria from BMS/Celgene, Janssen, Roche, AstraZeneca, Kite/Gilead and Abbvie. D.W.S. has received research funding from Roche/Genentech and Janssen, consultancy fees from AbbVie, AstraZeneca, Incyte, and Janssen and has patents and royalties with NIH and Nanostring. K.R. is an advisory board consultant for AstraZeneca, AbbVie and Janssen. L.H.S. has received research funding from Genentech Inc, F. Hoffmann-La Roche Ltd and Teva and honoraria from Amgen, AbbVie, Apobiologix, AstraZeneca, Genentech Inc, Acerta, Celgene, Janssen, Kite, Gilead, Karyopharm, Lundbeck, Merck, MorphoSys, F. Hoffmann-La Roche Ltd, Seattle Genetics, Teva, Takeda, Servier, Chugai, TG therapeutics and Verastem Oncology. C.L.T. has received research funding and honoraria from Janssen and AstraZeneca. A.S.G. has received research funding from Roche, AstraZeneca, AbbVie, and Janssen, and honoraria from Sandoz, AstraZeneca, AbbVie and Janssen. The remaining authors have no conflicts of interest to declare.

Additional information

Funding

R.S.K. was funded by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship – Master’s (CGS-M) and a UBC Hematology Research Program Research Grant. We acknowledge the following companies for providing funding for the BC CLL Provincial Database: AstraZeneca Canada, Janssen Inc., Abbvie Inc., GlaxoSmithKline (Canada) Inc., Gilead Canada Sciences, Inc., Lundbeck Canada Inc., and Roche Ltd. (Canada).