Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic-phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY

Rüdiger Hehlmann, Jorge E Cortes, Teresa Zyczynski, Carlo Gambacorti-Passerini, Stuart L Goldberg, Michael J Mauro, Mauricette Michallet, Bengt Simonsson, Loretta A Williams, Srikanth Gajavelli, Irene DeGutis, Ginny P Sen, Ron L Paquette, Rüdiger Hehlmann, Jorge E Cortes, Teresa Zyczynski, Carlo Gambacorti-Passerini, Stuart L Goldberg, Michael J Mauro, Mauricette Michallet, Bengt Simonsson, Loretta A Williams, Srikanth Gajavelli, Irene DeGutis, Ginny P Sen, Ron L Paquette

Abstract

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI.

Conflict of interest statement

RH has received consultancy fees from BMS and grants from Novartis. JC has received grants and/or consultancy fees from Ariad, BMS, Novartis, Pfizer and Teva. TZ, SG, and ID are employees of BMS. CGP has received grants and consultancy fees from BMS, and honoraria/grants from Pfizer. SLG has received grants and/or consultancy fees from BMS, Ariad, Novartis, and Pfizer. M Mauro has received grants from Novartis Oncology and Ariad/Takeda, and consultancy fees from BMS, Ariad/Takeda and Pfizer. M Michallet reports grants from BMS, consultant fees/honoraria from BMS, Pfizer, Novartis, Astellas Pharma, MSD and Genzyme. RP, BS, and LW declare no conflict of interest. AF and GS are employees of ICON Clinical Research.

© 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
A, Proportions of patients with 1 (left hand panel) or more than 1 (right hand panel) treatment interruption for patients who had a treatment interruption within 1 year (black bars) or within 1‐2 years (gray bars) of initiating first‐line TKI. B, Proportions of patients who discontinued TKI treatment within 2 years of first‐line TKI initiation, according to the time interval within which discontinuation occurred. Totals are given above each bar. C, Proportions of patients who switched from first‐line TKI to a second‐line TKI within 2 years of TKI treatment initiation, according to the time interval within which discontinuation occurred. Totals are given above each bar. D, Numbers of patients who switched from a first‐line TKI to one of the specified second‐line TKIs

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