Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients

• Published in: Blood cancer journal (New York) Vol. 8; no. 10; pp. 91 - 8
• Main Authors: Hernández-Boluda, Juan Carlos, Pereira, Arturo, Pastor-Galán, Irene, Alvarez-Larrán, Alberto, Savchuk, Alisa, Puerta, José Manuel, Sánchez-Pina, José María, Collado, Rosa, Díaz-González, Alvaro, Angona, Anna, Sagüés, Miguel, García-Gutiérrez, Valentín, Boqué, Concepción, Osorio, Santiago, Vallansot, Rolando, Palomera, Luis, Mendizábal, Arantxa, Casado, Luis Felipe, Pérez-Encinas, Manuel, Pérez-López, Raúl, Ferrer-Marín, Francisca, Sánchez-Guijo, Fermín, García, Carmen, Heras, Natalia de las, López-Lorenzo, José Luis, Cervantes, Francisco, Steegmann, Juan Luis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.12.2018; Springer Nature B.V
• Subjects: 692/699/1541/1990/2331; 692/700/565/1436/2185; Aged; Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - adverse effects; Anticarcinogenic Agents - therapeutic use; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical medicine; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - antagonists & inhibitors; Fusion Proteins, bcr-abl - genetics; Hematology; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Middle Aged; Oncology; Patients; Proportional Hazards Models; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Recurrence; Treatment Outcome
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-018-0125-0

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss ( n  = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR ( n  = 12), patient preference ( n  = 2), and withdrawal syndrome ( n  = 1). Treatment-free remission rate at 4 years was 64% (95% confidence interval, CI: 55%–72%). Cumulative incidence of molecular recurrence at 3 years was 33% (95% CI: 26%–38%). TKI treatment for < 5 years and MR4.5 duration shorter than 4 years were both associated with higher incidence of molecular recurrence. No patient had disease progression. Response status at last control was: MR4.5 ( n  = 196), MR4 ( n  = 15), MMR ( n  = 14), complete cytogenetic response ( n  = 10), and other ( n  = 1). A significant increase in Hb and cholesterol levels was observed after imatinib withdrawal. Our results demonstrate that TKI treatment discontinuation is feasible in real-life clinical practice.