Therapeutic Strategies and Outcomes in Patients with Chronic Myeloid Leukemia: A Real World Study

Introduction: The outcomes of patients with Chronic Myeloid Leukemia (CML) have dramatically changed with the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKI). Evidence from the real world can further assist in improving the care of patients with CML.

Methods: This is a retrospective multicenter study. We evaluated TKI treatment patterns and outcomes of patients with CML in two middle-size European countries with different healthcare systems. Patients from 9 centers in the Czech Republic and Greece with Philadelphia chromosome-positive CML in chronic phase, who received treatment with a TKI between 2010 and 2017 were included in the study. Patients treated exclusively in clinical trials and/or expressing atypical transcripts were excluded from this analysis.

A customized data management system was developed for the collection and management of the data, including a database for the storage of data, designed and implemented for patients with CML (CML database). Collected data from different medical centers were transformed in the defined format, homogenized and integrated into the CML database.

The primary objective of the study was to evaluate TKI treatment patterns and sequences in the real world during the study period. Secondary objectives included describing the overall survival (OS), and reasons for treatment discontinuation, and identifying risk factors that may impact OS.

Results: A total of 1360 patients were included. Most were males (712, 52.4%), with a median age of 56 years [interquartile range (IQR): 42-66]. Most patients (566, 84.9%) had a low EUTOS score at diagnosis. P210 was the most common type of BCR::ABL1 protein and e14a2 was the most common transcript [1209 (99%) and 764 (62.1%), respectively].

The median follow-up of the entire cohort was 11.3 years (95% confidence intervals (CI): 11-12) and the median of total lines of treatment was 1 (IQR 1-2). In first-line treatment, imatinib, nilotinib, interferon, and dasatinib, were administered in 74.8%, 13%, 7.8%, and 4.4%, respectively.

Deep molecular response (DMR), major molecular response (MMR) and <MMR were achieved in 641 (71.7%), 198 (22.1%) and 55 (6.2%) patients, respectively. DMR rates in patients treated with dasatinib, imatinib and nilotinib were 78%, 70% and 74.2%, respectively.

Failure (191, 14%) and toxicity (105, 7.7%) were the main reasons for permanent treatment discontinuation.

Forty-nine (3.6%) patients progressed to blast crisis or accelerated phase and 62 (4.5%) patients were treated with allogeneic stem cell transplantation after a median of 3 treatment lines.

Due to many censored cases and some events occurring after 20 years of follow-up, the OS of the entire cohort was 22.75 years (95% CI: 21.4-not-estimable). The estimated 10-year survival rate was 79.1%. In multivariate analysis, younger age (hazard ratio (HR): 1.07, 95% CI: 1.05-1.09, p<0.001) and lower EUTOS score (HR: 0.58, 95% CI: 0.34-0.99, p=0.044) were the only statistically significant protective factors from death. The type of treatment and country did not impact OS.

Conclusion: Confirming the findings of previous studies, patient and disease characteristics were better predictors of OS than first-line treatment in patients with CML treated with TKIs.

Acknowledgement: This study was financially supported in part by Novartis.

Chatzikonstantinou:AbbVie: Honoraria. Stamatopoulos:Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Novartis: Research Funding; Roche: Research Funding; Bristol Myers Squibb: Honoraria; Lilly: Honoraria; AbbVie: Honoraria, Research Funding. Mayer:Novartis: Research Funding; AstraZeneca: Research Funding; AOP Health: Research Funding; Merck & Co., Inc., Rahway, NJ, USA: Research Funding.