PMID- 37033642 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230411 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 14 DP - 2023 TI - Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study. PG - 1154377 LID - 10.3389/fphar.2023.1154377 [doi] LID - 1154377 AB - TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate. CI - Copyright (c) 2023 Iurlo, Cattaneo, Consonni, Castagnetti, Miggiano, Binotto, Bonifacio, Rege-Cambrin, Tiribelli, Lunghi, Gozzini, Pregno, Abruzzese, Capodanno, Bucelli, Pizzuti, Artuso, Iezza, Scalzulli, La Barba, Maggi, Russo, Elena, Scortechini, Tafuri, Latagliata, Caocci, Bocchia, Galimberti, Luciano, Fava, Foa, Saglio, Rosti and Breccia. FAU - Iurlo, A AU - Iurlo A AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Cattaneo, D AU - Cattaneo D AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Consonni, D AU - Consonni D AD - Epidemiology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Castagnetti, F AU - Castagnetti F AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seragnoli", University of Bologna, "S. Orsola-Malpighi" Hospital, Bologna, Italy. FAU - Miggiano, M C AU - Miggiano MC AD - Division of Hematology, San Bortolo Hospital, Vicenza, Italy. FAU - Binotto, G AU - Binotto G AD - Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy. FAU - Bonifacio, M AU - Bonifacio M AD - Department of Medicine, Section of Hematology, University of Verona, Verona, Italy. FAU - Rege-Cambrin, G AU - Rege-Cambrin G AD - Division of Internal Medicine and Hematology, San Luigi Gonzaga Hospital, Turin, Italy. FAU - Tiribelli, M AU - Tiribelli M AD - Division of Hematology and BMT-Udine Hopsital, ASUFC and Department of Medicine-University of Udine, Udine, Italy. FAU - Lunghi, F AU - Lunghi F AD - Division of Hematology and BMT, IRCCS San Raffaele Hospital, Milan, Italy. FAU - Gozzini, A AU - Gozzini A AD - Division of Hematology, AOU Careggi, Firenze, Italy. FAU - Pregno, P AU - Pregno P AD - Division of Hematology, AOU Citta della Salute e della Scienza, Torino, Italy. FAU - Abruzzese, E AU - Abruzzese E AD - Hematology Division, Sant'Eugenio Hospital, Rome, Italy. FAU - Capodanno, I AU - Capodanno I AD - Division of Hematology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. FAU - Bucelli, C AU - Bucelli C AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Pizzuti, M AU - Pizzuti M AD - Hematology Unit, Ospedale Potenza, Potenza, Italy. FAU - Artuso, S AU - Artuso S AD - Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Iezza, M AU - Iezza M AD - Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "L. and A. Seragnoli", University of Bologna, "S. Orsola-Malpighi" Hospital, Bologna, Italy. FAU - Scalzulli, E AU - Scalzulli E AD - Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy. FAU - La Barba, G AU - La Barba G AD - Hematology Unit, Azienda USL di Pescara, Pescara, Italy. FAU - Maggi, A AU - Maggi A AD - Division of Hematology, Hospital "S. G. Moscati", Taranto, Italy. FAU - Russo, S AU - Russo S AD - Division of Hematology, Dipartimento di Patologia Umana dell''Adulto e dell'Eta Evolutiva, Policlinico G. Martino, University of Messina, Messina, Italy. FAU - Elena, C AU - Elena C AD - UOC Ematologia 1, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. FAU - Scortechini, A R AU - Scortechini AR AD - Division of Hematology, Department of Molecular and Clinical Sciences, Polytechnic University of Marche, Ancona, Italy. FAU - Tafuri, A AU - Tafuri A AD - Division of Hematology, Azienda Ospedaliera Universitaria Sant'Andrea, Rome, Italy. FAU - Latagliata, R AU - Latagliata R AD - Division of Hematology, Belcolle Hospital, Viterbo, Italy. FAU - Caocci, G AU - Caocci G AD - Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy. FAU - Bocchia, M AU - Bocchia M AD - Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy. FAU - Galimberti, S AU - Galimberti S AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Luciano, L AU - Luciano L AD - Division of Hematology, Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy. FAU - Fava, C AU - Fava C AD - Department of Clinical and Biological Sciences, University of Torino, Torino, Italy. FAU - Foa, R AU - Foa R AD - Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy. FAU - Saglio, G AU - Saglio G AD - Department of Clinical and Biological Sciences, University of Torino, Torino, Italy. FAU - Rosti, G AU - Rosti G AD - Scientific Direction, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy. FAU - Breccia, M AU - Breccia M AD - Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy. LA - eng PT - Journal Article DEP - 20230323 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC10076530 OTO - NOTNLM OT - chronic myeloid leukemia OT - low dose OT - outcome OT - resistance OT - treatment-free remission OT - tyrosine kinase inhibitors COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/04/11 06:00 MHDA- 2023/04/11 06:01 PMCR- 2023/03/23 CRDT- 2023/04/10 03:55 PHST- 2023/01/30 00:00 [received] PHST- 2023/03/14 00:00 [accepted] PHST- 2023/04/11 06:01 [medline] PHST- 2023/04/10 03:55 [entrez] PHST- 2023/04/11 06:00 [pubmed] PHST- 2023/03/23 00:00 [pmc-release] AID - 1154377 [pii] AID - 10.3389/fphar.2023.1154377 [doi] PST - epublish SO - Front Pharmacol. 2023 Mar 23;14:1154377. doi: 10.3389/fphar.2023.1154377. eCollection 2023.