Patterns of Tyrosine Kinase Inhibitor Utilization in Newly Treated Patients With Chronic Myeloid Leukemia: An Exhaustive Population-Based Study in France

Abstract

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions.

Incident users of tyrosine kinase inhibitors in patients with chronic myeloid leukemia: Analysis of anticancer treatment trajectories—A French population‐based study using the French national health data system

“…Due to resistance or adverse drug reactions, other drugs have been developed for this indication: dasatinib and nilotinib, both recommended for first‐line treatment (LT) by the European LeukemiaNet (ELN), bosutinib, and ponatinib 2 . Few data are available regarding the real‐life use of TKIs for CML, especially on the entire population of a country, but these data can provide a description of care pathways, which are sometimes complex in real‐life conditions 3–5 …”

“…2 Few data are available regarding the real-life use of TKIs for CML, especially on the entire population of a country, but these data can provide a description of care pathways, which are sometimes complex in real-life conditions. [3][4][5] The objective of this study was to describe TKI treatment courses in patients with CML who initiated treatment between 2014 and 2017 and who were followed for 3 years, using data from the French Health Data System (SNDS).…”

“…In this study, TKI LT initiation in new patients with CML is consistent with a previous SNDS study (2011-2014) and with ELN recommendations (2013). 2,5 Imatinib and nilotinib accounted for 95% of the initial treatments, while dasatinib was not legally reimbursed in 1-LT in France but was mainly used in 2-LT. While the rate of initial imatinib prescription is the same across studies (approximately 80% of the patients), the TKI used in 2-LT differs according to the country: either nilotinib was the main TKI used in 2-LT, or nilotinib and dasatinib were used at equal rates for 2-LT. 3,5 Characteristics of the CML population described in our study are similar to the CML population in a French cancer registry in terms of age and gender ratio (median age of 62 years and 56% male) and is consistent with the incidence rate in France.…”

“…2,5 Imatinib and nilotinib accounted for 95% of the initial treatments, while dasatinib was not legally reimbursed in 1-LT in France but was mainly used in 2-LT. While the rate of initial imatinib prescription is the same across studies (approximately 80% of the patients), the TKI used in 2-LT differs according to the country: either nilotinib was the main TKI used in 2-LT, or nilotinib and dasatinib were used at equal rates for 2-LT. 3,5 Characteristics of the CML population described in our study are similar to the CML population in a French cancer registry in terms of age and gender ratio (median age of 62 years and 56% male) and is consistent with the incidence rate in France. 1 1-LT imatinib patients were older and had more comorbidities than 1-LT nilotinib patients, which is consistent with other studies and recommendations since imatinib is a safer option for patients with comorbidities, although it may be less potent.…”

“…We used an identification algorithm previously used and similar to another which has been validated to identify patients with CML in this database. 5,6 Exposure to drugs was identified through reimbursement data prospectively collected, thereby avoiding recall and misclassification biases. We had no information on drug administration, but chronic use of this treatment with a dispensation every month substantially limits this type of bias.…”