Ponatinib as a consolidation strategy for a second attempt at TKI discontinuation in chronic myeloid leukemia: Interim results from the restop Trial
Year: 2025
Type: conference-abstract
Abstract: INTRODUCTIONApproximately 30–50% of patients with chronic myeloid leukemia (CML) are eligible for tyrosine kinase inhibitor (TKI) discontinuation, of whom only 50–60% achieve sustained treatment-free remission (TFR). This rate decreases to 20–30% in published series on second TKI discontinuation attempts. The potency of the third-generation TKI ponatinib makes it a promising candidate to deepen molecular response prior to a second discontinuation attempt. METHODSResToP is a phase II, multicenter, open-label, non-comparative clinical trial that enrolled adult patients with chronic-phase CML who had previously failed a first TKI discontinuation attempt and had subsequently regained a sustained deep molecular response (MR4) for ≥1 year after restarting therapy. Patients received consolidation therapy with ponatinib 15 mg/day and acetylsalicylic acid 100 mg/day for 2 years, followed by complete treatment withdrawal. Molecular response was monitored via monthly BCR::ABL1 RT-qPCR for the first 28 weeks, then every 3 months until completing 52 weeks post-discontinuation. (NCT04160546)The primary objective of the study was to evaluate the proportion of patients maintaining a major molecular response (MMR) during the 52 weeks following ponatinib discontinuation. Secondary objectives included safety and tolerability, MR4 maintenance rate, and progression-free survival (PFS). RESULTSA total of 40 patients were enrolled between 2020 and 2022; 34 started ponatinib therapy, of whom 12 discontinued treatment early (9 due to treatment-related adverse events, and 3 due to unrelated causes). In the interim analysis, 1 patient remained on ponatinib, and 21 had entered the treatment-free phase.With a median follow-up of 49.7 weeks post-discontinuation, 85.7% of patients maintained MMR and 61.9% maintained MR4, with an overall TFR rate of 81%. No progressions to accelerated or blast phase were observed.A total of 26 patients (76.5%) reported ponatinib-related adverse events, including 17.6% with grade ≥3 events, such as 3 grade-3 cardiovascular events (stroke, myocardial infarction, and peripheral ischemia). Two of these patients had predisposing risk factors. The most frequent grade 1–2 toxicities were hypertension (14.7%), hepatotoxicity, arthralgia, and myalgia (each at 11.8%). One death unrelated to therapy was recorded. CONCLUSIONConsolidation therapy with ponatinib represents an effective and safe strategy for a second TKI discontinuation in CML patients after a prior failed withdrawal attempt.
Source: Blood
Authors: Almudena Zaratiegui Vergara, Gonzalo Carreño, Francisca Ferrer Marin, Blanca Xicoy, María Teresa Gómez Casares, Fermin Sanchez-Guijo, M Concepción Ruiz Nuño, Santiago Osorio Prendes, Raquel De Paz, Ana Isabel Rosell Mas, Elvira Mora Casterá, María Alicia Senin, Juan Carlos Hernandez Boluda, Rosa Ayala Diaz, Valentín García Gutiérrez, Joaquin Martinez Lopez
Institutions: Hospital Universitario 12 De Octubre, Hospital General Universitario Morales Meseguer, Institut Català d'Oncologia, Hospital Universitario de Gran Canaria Doctor Negrín, Complejo Hospitalario de Salamanca, Hospital Regional Universitario de Málaga, Hospital General Universitario Gregorio Marañón, Hospital Universitario La Paz, Hospital Clínico Universitario Virgen de la Victoria, Hospital Universitari i Politècnic La Fe, Duran i Reynals Hospital, Hospital Clínico Universitario de Valencia, Hospital Universitario Ramón y Cajal
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417021561
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