A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia

Abstract

Background The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. Methods This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. Results Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. Conclusions Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice.

Value of combining biological age with assessment of individual frailty to optimize management of cancer treated with targeted therapies: model of chronic myeloid leukemia treated with tyrosine kinase inhibitors (BIO-TIMER trial)

“…Furthermore, given the data reported in the literature [21] and data from CML Observatory, it seems reasonable to expect 35% TKI intolerance. Thus, an enrolment of 321 patients will enable us to identify a 15% absolute…”

Chronic Myeloid Leukaemia: A Qualitative Study of Patient and Practitioner Experiences of Managing Treatment

“…Use of European Leukaemia Network (ELN) treatment guidance [3] was common amongst the HCPs we interviewed. Some studies have, however, questioned the "real world" applicability of such guidance, for example in the areas where HCPs fail to comply with ELN and National Comprehensive Cancer Network guidelines [48], and raised concerns about suboptimal monitoring, inadequate cardiovascular risk assessment and multiple TKI switches [49,50]. Regarding treatment decisions, a lack of trials comparing second-line TKI drugs to each other, along with their difering side efect profles, means the decision can be complex and based on individual patients' risk and tolerability [3,51].…”