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3174 Tyrosine Kinase Inhibitor (TKI) Treatment Patterns in 5,261 Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients in “Real-Life” Settings: A Population-Based Study Using a Nationwide Claim Database

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
CML, Chronic Myeloid Malignancies, Diseases, therapy sequence, Therapies, Myeloid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Meriem Benmerad, MSc, DipEng1*, Jules Chassetuillier, DipEng1*, Christophe Bouvier, DM2,3*, Pierre-Louis Lecoq, MSc4*, Romain Favier, PharmD4*, Matthieu Trancart, MSc, Eng4*, Sandrine Hayette, PhD3,5*, Julien Bollard, PhD6*, Audrey Lajoinie1* and Franck E. Nicolini, MD, PhD7,8

1RCTS, Lyon, France
2Equipe Evaluation Médicale et Sarcomes (EMS), Centre Léon Bérard, Lyon, France
3Fi-LMC, Lyon, France
4Novartis Pharma S.A.S, Rueil Malmaison, France
5Laboratory of Hematology, Centre Hospitalier Lyon Sud, Pierre Benite, FRA
6Hematology Department, Centre Leon Berard, Lyon, France
7Hematology department & CRCL INSERM U1052, Centre Léon Bérard, Lyon, France
8Fi-LMC group, Lyon, France


The introduction of TKI in CP-CML enabled responders to reach a similar survival to that of the general population. However, recent small-sized real-life studies showed that 1 in 5 CP-CML patients (pts) received at least 3 lines of TKI, mainly due to resistance or the onset of adverse events (AE). The objective of this study is to document real-life TKI treatment patterns nationwide in CML pts with a long-term follow-up, with a focus on pts who initiated at least a 3rd line and associated disease burden.


This real-life non-interventional study was conducted using the French nationwide claim database (SNDS, Système National des Données de Santé), covering over 99% of French beneficiaries. Pts who initiated their first TKI with an indication for CML (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) between January 2010 and December 2018, aged 18 years old or older at TKI initiation (index date T0), and with healthcare resource use (HCRU) markers of CML – i.e., reasons for hospitalization and reported Long-Term Disease - without markers of confounding disease for the use of TKIs, were included. Treatment patterns were assessed from T0 to December 2020 or death, through the description of TKI treatment sequences (TKI lines), adherence – discontinuations (≥ 3 months) during a TKI line and Medication Possession Ratio (MPR) –, and line duration (Time to Next Treatment (TTNT) estimates). TTNT was calculated as cumulative incidence of TKI switches, with death as competing risk; switches were defined as discontinuation of a TKI followed by the start of a different TKI.


A total of 5,261 CML pts initiated their 1st line TKI, with a median age at T0 of 59.5 years (IQR: 23.2) and a M/F ratio of 1.2. The median follow-up from T0 was 5.6 years (IQR: 4.6). Respectively 2,299, 1,017 and 426 pts initiated 2nd, 3rd and 4th TKI line. Most frequent TKIs used as 1st and 2nd lines were imatinib (73.1%), and dasatinib (60.4%; Figure 1), respectively. From the 3rd line, TKI patterns changed following the reimbursement of bosutinib in 2015 and ponatinib in 2016, and subsequently stabilized; shares in pts treated in 3rd line and more at the beginning of 2020 were roughly equally distributed between marketed TKIs.

TKI discontinuations rates during a line varied from 76.2% for 1st line to 56.2% for 4th lines. The median cumulative duration of discontinuations tended to decrease across lines (2.9, 2.5, 2.3 and 2.1 months for 1st, 2nd, 3rd, and 4th line, respectively); IQRs across lines were similar. The proportion of pts with a good medication adherence (MPR ≥ 80%) was around 80% for all TKI lines.

TTNT was similar across all TKIs and all lines; 10-year TTNT rates were 48% (95CI: [47%; 50%]), 56% [53%; 59%], 56% [51%; 61%], 48% [42%; 54%] for 1st, 2nd, 3rd, and 4th lines. For pts who switched, most of switches occurred during the first year following line initiation (51% of switches observed in the first year for both 1st, 2nd, 3rd, and 4th lines), 24% occurred during the second year, and 10% during the third year. The 10-year cumulative incidences of death were 12% (95CI: [11%; 14%]), 9% [8%; 11%], 12% [9%; 16%], 14% [6%; 25%] for 1st, 2nd, 3rd, and 4th lines, respectively.

The proportion of CML pts who initiated at least 3 lines of TKIs was 19.3% from raw estimates (n=1,017/5,261) and would be 27% based on TTNT estimates. Their characteristics were similar to pts who initiated 1st line TKI (sociodemographic, comorbidities). Regarding HCRU, respectively 37.2% and 29.8% of pts had at least one hospitalization during 1st and 6th semesters following 3rd line initiation; 7.9% to 5.8% visited emergency room, and around 10% had at least one sick leave per semester.


Using one of the largest cohorts of CML pts ever studied, with a follow-up period up to 10 years (median 5.6 years), this real-life study confirmed that multiple TKI switches are now common. We confirmed that at least 1 out of 5 CML patient fails at least two TKI lines. From TTNT estimates, surrogate marker for the duration of clinical benefit, lines of TKI would be effective over the long-term for around half of pts, and half of the switches occur within the first two years, regardless of line position. Finally, this real-world study illustrates the need for permanent care of these pts and alternative treatment options to avoid resistance or intolerance and induce a similar survival as the general population of the same age.

Disclosures: Benmerad: Novartis: Other: service provider as a Contract Research Organization. Chassetuillier: Novartis: Other: service provider as a Contract Research Organization. Lecoq: Novartis: Current Employment. Favier: Novartis: Current Employment. Trancart: Novartis: Current Employment. Lajoinie: Novartis: Other: service provider as a Contract Research Organization. Nicolini: SUN pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; INCYTE BIOSCIENCES: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH