PS1182 REAL WORLD TYROSINE KINASE INHIBITOR TREATMENT PATHWAYS, MONITORING PATTERNS AND RESPONSES COMPARED WITH ELN RECOMMENDATIONS IN CHRONIC MYELOID LEUKAEMIA: FINAL ANALYSIS OF THE UK TARGET CML STUDY
Authors: D. Milojkovic, N.C. Cross, S. Ali, J.L. Byrne, G. Campbell, F.L. Dignan, L. Fildes, M.‐F. McMullin, P. Neelakantan, M. Sivakumaran, F. Wandroo, F. Willis, J. Ryan, R.E. Clark, A. Mead
Journal: HemaSphere (2019)

Background: Response to tyrosine kinase inhibitor (TKI) treatment is a key predictor of outcome in chronic myeloid leukaemia (CML), as outlined in the European LeukemiaNet recommendations in 2013 [ELN2013]. ELN2013 define responses as “optimal”, “warning” or “failure” at specific milestones to guide TKI therapy switch. However, it is unclear how ELN2013 are implemented in routine clinical practice. In addition, the documentation of clinical characteristics, such as cardiovascular (CV) risk factors, which might impact treatment decisions in real world practice is not well understood. Furthermore, achievement of deep molecular response (DMR; BCR‐ABL1IS ≤0.01%) a goal for treatment‐free remission, outside of trials is not well described. Here we report the final results for the UK TARGET CML study of real world management of CML and the observed outcomes. Aims: Evaluate TKI treatment pathways, monitoring patterns and responses in UK patients (Pts) with CML against ELN2013 to inform future clinical practice. Methods: Retrospective observational study (sponsor Novartis UK) at 21 UK centres; Pt characteristics, TKI choice and responses were collected with consent by medical record review in 257 adult chronic phase CML Pt (≥18 years (y)). Data was analysed using descriptive statistics when all Pts had ≥13 months (m) follow‐up (final data cutoff June 6, 2018). Results: Median (mdn) follow‐up of all 257 Pts was 33m (range [r] 13–59m); mdn age 53.5y (r 18–92y) (144[56%] were male). Sokal and EUTOS score, documented in 96/257 and 36/257 respectively, appeared not to influence TKI choice (31/42 high risk Sokal Pts received first‐line (1L) imatinib). Most Pts (203/257) received 1L imatinib (50 nilotinib, 4 dasatinib). Pts receiving second generation (2G) TKI were younger (mdn age imatinib 55y [r 18–92y] versus 2GTKI 46y [r 20–79.5y]). Overall 149/257 (58%) had ≥1 recorded baseline comorbidity (81/257 with CV comorbidities). Several CV risk factors were poorly documented at baseline for all Pts including blood pressure (74/257), blood glucose (60/257), and cholesterol (40/257) (documentation prior to 1L 2GTKI use was 12/54, 20/54, and 11/54, respectively). Also CV risk assessment tools such as “QRISK2” were poorly documented (3/257). Frequency of 1L molecular or cytogenetic assessments was 83% (186/223), 76% (151/199), and 69% (117/170) at 3, 6, and 12m respectively. An ELN failure response was observed in 48/223, and post failure 11/48 remained on 1L with median follow‐up post failure of 14m (r 6–34m). Overall 113/257 (44%) switched TKI at least once (54/257 (21%) &gt;1 switch). Main reasons for switch from 1L were resistance (73/113 [mutation analysis was performed in 20/73 prior to switch]) and intolerance (38/113). On second‐line (2L), frequency of response testing at 3, 6, and 12m was 79% (65/82), 68% (45/66) and 52% (27/52), respectively. Overall 10/257 Pts had disease progression (1L imatinib n = 9; 1L 2GTKI n = 1). Table 1 summarises observed responses. Summary/Conclusion: In this real‐world UK cohort with mdn follow‐up of &lt;3y, 44% of patients switched TKI at least once. DMR was observed in real world practice even in Pts switching TKI following an ELN failure or documented resistance. The final findings demonstrate ELN2013 are not universally implemented in UK practice with respect to the timing of monitoring, performance of mutational analysis, and management of Pts with an ELN failure. In addition we now also report that important baseline data such as CV risk factors were poorly documented, highlighting key areas for improvement for optimal Pt management in the UK. image