High Level of Successful TKI Discontinuation in Chronic Myeloid Leukemia (CML) Patients: Preliminary Results of AST-Argentina Stop Trial

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.3-5
• Main Authors: Pavlovsky, Carolina, Varela, Ana Ines, Fernandez, Isolda I., Sanchez, Maria Belen, Custidiano, Maria Del Rosario, Freitas, Josefina, Ventriglia, Veronica, Garcia de Labanca, Ana, Bendek, Georgina, Mariano, Romina, Levy, Estrella, Vera, Masiel, Giere, Isabel, Vasconcelos Cordoba, Bianca, Mela Osorio, María Jose, Pavlovsky, Miguel A., Sanchez Avalos, Julio Cesar, Foncouberta, Cecilia, Juni, Mariana, Riddick, Maximiliano, Bianchini, Michele, Moiraghi, Beatriz
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-142416

Introduction: Treatment-free remission (TFR) is an emerging treatment goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). Current evidence shows that 40%-60% of patients relapse while in TFR; and nearly all regain response once tyrosine kinase inhibitors (TKIs) treatment are reinitiated. However a robust predictor of prolonged TFR has not been reported yet. Considering real-life setting, 2 key factors may affect TFR outcome if not properly done: Access to serial molecular monitoring at optimal timepoints and quality laboratory terms as accuracy, sensitivity and rapid results. This motivated the creation of the AST study in our region to guarantee adequate molecular monitoring for TFR in Argentina and characterize new prognostic biomarkers helpful to identify more accurately patients who will be able to sustain TFR. We aimed to assess the proportion of patients with sustained major molecular response (MMR) after TKIs discontinuation and define precise conditions for stopping treatment. Methods: This prospective, multicentre Argentina Stop Trial (AST) trial is recruiting chronic phase CML patients under TKI treatment for at least ≥ 4 years, in DMR (≥MR4.0) sustained for ≥ 2 years in standardized laboratory, confirmed typical BCR-ABL1 transcripts b3a2 and/or b2a2 and aged > 18 years. Molecular tests are centralized in 2 harmonized laboratories and performed monthly for the first 6 months, every 2 months until the first year, and every 3 months during the second year. If patients lost MMR, TKI was restarted immediately. Molecular relapse Free Survival was estimated by Kaplan-Meier method. Difference between survival variables was evaluated through log-rank test. Multivariate analysis was performed through Cox proportional hazards model. The cutoffs of the numerical variables were considered according to the log-rank test. Results: Between February 2019 and July 2020, we evaluated 50 CML patients of whom 46 were enrolled from 7 centers in Argentina and 4 were screening failures. Recruitment was interrupted due to COVID-19 pandemic. Patient median age was 57.5 years (range 24-85). Before discontinuation, TKI treatment was as follows: Imatinib 37/46 (80%), Nilotinib 5/46 (11%) and Dasatinib 4/46 (9%), 2G-TKI as 1st line, 11% of the patients received non-branded treatment. Sokal risk score showed to be low in 22 patients (48%), intermediate in 14 (30%) and high in 10 (22%). Median follow-up was 10 months (range 4-17) and the estimate