Patients with chronic lymphocytic leukemia (CLL) who discontinue tyrosine kinase inhibitor (TKI) therapy due to toxicity can successfully be treated with an alternate TKI, and may even achieve durable responses, according to a study published in Blood.1

Practice patterns after TKI discontinuation and optimal sequencing remain unclear. Researchers retrospectively analyzed data from patients with CLL who discontinued ibrutinib or idelalisib.

Among the 178 patients included, 62% achieved a response to the first TKI; 14% had a complete response. Median progression-free survival and overall survival from the time of first TKI initiation were 10.5 months and 29 months, respectively.

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TKI discontinuation was most commonly due to toxicity (51%), disease progression (29%), and Richter transformation (8%).

Initial TKI choice was not associated with progression-free survival or overall survival, though Richter transformation reduced patient survival rates.

A total of 114 patients receive salvage therapy following the discontinuation of their first TKI. The overall response rate to subsequent TKI therapy was 50%, with a median progression-free survival of 11.9 months.

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Median progression-free survival was not reached among patients intolerant to their first TKI who were treated with an alternate TKI, in contrast with 7 months among those who discontinued therapy due to CLL progression.


  1. Mato AR, Nabhan C, Barr PM, et al. Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience. Blood. 2016 Sep 7. doi: 10.1182/blood-2016-05-716977 [Epub ahead of print]