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Blood. 2016 Nov 3;128(18):2199-2205. Epub 2016 Sep 6.

Outcomes of CLL patients treated with sequential kinase inhibitor therapy: a real world experience.

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Center for Chronic Lymphocytic Leukemia, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
University of Chicago Comprehensive Cancer Center, Chicago, IL.
Wilmot Cancer Institute, University of Rochester, Rochester, NY.
Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY.
John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ.
Penn State Cancer Institute, Penn State University, Hershey, PA.
University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA.
Tufts University Medical Center, Boston, MA; and.
Celgene Corporation, Summit, NJ.


B-cell receptor kinase inhibitor (KI) therapy represents a paradigm shift in chronic lymphocytic leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who discontinued KI therapy. We examined responses, toxicity, post-KI therapies, and overall survival (OS). Patients had a median of 3 prior therapies (range 0-11); del17p (34%), p53 mutation (27%), del11q (33%), and complex karyotype (29%). Overall response rate (ORR) to first KI was 62% (complete response 14%). The most common reasons for KI discontinuation were toxicity (51%), CLL progression (29%), and Richter transformation (RT) (8%). Median progression-free survival (PFS) and OS from KI initiation were 10.5 and 29 months, respectively. Notably, initial KI choice did not impact PFS or OS; however, RT portended significantly inferior OS (P = .0007). One hundred fourteen patients received subsequent salvage therapy following KI discontinuation with an ORR to subsequent KI at 50% and a median PFS of 11.9 months. Median PFS in KI-intolerant patients treated with an alternate KI was not reached vs 7 months for patients with CLL progression. In summary, these data demonstrate that toxicity was the most common reason for KI discontinuation, that patients who discontinue KI due to toxicity can respond to an alternate KI, and that these responses may be durable. This trial was registered at as #NCT02717611 and #NCT02742090.

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