C069 | Second Attempt to Discontinue Tki After Molecular Relapse in Chronic Myeloid Leukemia Patients: a Real-life Italian Multicenter Study
Year: 2025
Type: article
Abstract: Approximately half of CML patients (pts) who attempted TKI discontinuation for the first time experienced a molecular relapse and restarted TKIs. Although there are several studies investigating first TFR attempt (TFR1), the plausibility and predictors for a second TFR (TFR2) have yet to be reported, with very few previously published studies. Currently, it is uncertain whether pts experiencing molecular relapse after TFR1 attempt may hope to reattempt TFR, with very limited data on parameters that can predict a successful TFR2. To evaluate the feasibility and likelihood of TFR2 success in real-life, we analyzed 83 chronic phase (CP)-CML pts regularly followed in 21 Italian hematological centers. At the time of CML diagnosis, median age was 47.3 years. Most pts were treated with first-line imatinib (59/83), while others with a second-generation (2G) TKI (24/83, including dasatinib in 5 cases and nilotinib in 19). Prior to TFR1 attempt, 21 cases had received second- or third-line therapy (including 16 pts resistant to prior TKIs), with a median TKI treatment duration of 6.7 years. At the time of TFR1, 81 (97.6%) pts had already achieved a deep molecular response (DMR), with a median duration of 4.1 years. During TFR1 attempt, all pts experienced a molecular relapse. The reason for TKI reintroduction was major molecular response (MMR) loss in all cases. At TFR2 attempt, 67 (80.7%) pts were on treatment with the same TKI as at TFR1: overall, imatinib in 38 pts and a 2G-TKI (dasatinib, nilotinib or bosutinib) in the remaining 45 pts, with a median duration before TFR2 of 4.4 years (range, 0.6-8.9). At the time of TFR2, 81 (97.6%) pts had already achieved a DMR, with a median duration of 3.2 years (range, 0.6-8.2). 42 pts (50.6%) lost MMR after a median of 4.1 months off therapy (range, 1.9-41.5), while 41 pts (49.4%) did not lose MMR and remained treatment-free for a median of 26.9 months (range, 0.6-131.2). The peak of molecular relapses occurred in the first year of TFR2. All the cases who experienced a molecular relapse restarted TKI treatments and regained at least an MMR within a median of 5 months from TKI resumption. At last follow-up, 3 pts died from CML-unrelated causes, while the others were alive. Furthermore, no cases of disease progression were recorded. This real-life study provides further information to support the safety of a second effort to stop TKI use in CP-CML pts, as a failed first attempt does not seem to prevent a second successful one.
Authors: A. Iurlo, D. Cattaneo, C. Fava, F. Castagnetti, M. Bonifacio, M. C. Miggiano, M. D’adda, I. Capodanno, C. Elena, L. Levato, A. R. Scortechini, F. Lunghi, M. Caramella, V. Bellani, V. Bonuomo, S. Grano, G. Cotilli, E. Scalzulli, M. Dalmazzo, S. Leonetti Crescenzi, L. Luciano, B. Martino, T. Intermesoli, D. Rapezzi, G. Binotto, M. Tiribelli, G. Saglio, C. Gambacorti-Passerini, M. Breccia, G. Rosti
Institutions: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, University of Turin, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, University of Verona, Ospedale San Bortolo, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Policlinico San Matteo Fondazione, Marche Polytechnic University, IRCCS Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, University of Milano-Bicocca, Sapienza University of Rome, Ospedale San Luigi Gonzaga, Federico II University Hospital, University of Naples Federico II, Azienda ospedaliera "Bianchi-Melacrino-Morelli", Ospedale Papa Giovanni XXIII, Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo, University of Padua, Azienda Ospedale - Università Padova, University of Udine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123096
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