Frontiers in Pharmacology (Mar 2023)
Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study
- A. Iurlo,
- D. Cattaneo,
- D. Cattaneo,
- D. Consonni,
- F. Castagnetti,
- M. C. Miggiano,
- G. Binotto,
- M. Bonifacio,
- G. Rege-Cambrin,
- M. Tiribelli,
- F. Lunghi,
- A. Gozzini,
- P. Pregno,
- E. Abruzzese,
- I. Capodanno,
- C. Bucelli,
- M. Pizzuti,
- S. Artuso,
- M. Iezza,
- E. Scalzulli,
- G. La Barba,
- A. Maggi,
- S. Russo,
- C. Elena,
- A. R. Scortechini,
- A. Tafuri,
- R. Latagliata,
- G. Caocci,
- M. Bocchia,
- S. Galimberti,
- L. Luciano,
- C. Fava,
- R. Foà,
- G. Saglio,
- G. Rosti,
- M. Breccia
Affiliations
- A. Iurlo
- Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- D. Cattaneo
- Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- D. Cattaneo
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- D. Consonni
- Epidemiology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- F. Castagnetti
- Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. and A. Seràgnoli”, University of Bologna, “S. Orsola-Malpighi” Hospital, Bologna, Italy
- M. C. Miggiano
- Division of Hematology, San Bortolo Hospital, Vicenza, Italy
- G. Binotto
- Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
- M. Bonifacio
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
- G. Rege-Cambrin
- Division of Internal Medicine and Hematology, San Luigi Gonzaga Hospital, Turin, Italy
- M. Tiribelli
- Division of Hematology and BMT—Udine Hopsital, ASUFC and Department of Medicine—University of Udine, Udine, Italy
- F. Lunghi
- 0Division of Hematology and BMT, IRCCS San Raffaele Hospital, Milan, Italy
- A. Gozzini
- 1Division of Hematology, AOU Careggi, Firenze, Italy
- P. Pregno
- 2Division of Hematology, AOU Città della Salute e della Scienza, Torino, Italy
- E. Abruzzese
- 3Hematology Division, Sant’Eugenio Hospital, Rome, Italy
- I. Capodanno
- 4Division of Hematology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
- C. Bucelli
- Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- M. Pizzuti
- 5Hematology Unit, Ospedale Potenza, Potenza, Italy
- S. Artuso
- Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- M. Iezza
- Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “L. and A. Seràgnoli”, University of Bologna, “S. Orsola-Malpighi” Hospital, Bologna, Italy
- E. Scalzulli
- 6Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy
- G. La Barba
- 7Hematology Unit, Azienda USL di Pescara, Pescara, Italy
- A. Maggi
- 8Division of Hematology, Hospital “S. G. Moscati”, Taranto, Italy
- S. Russo
- 9Division of Hematology, Dipartimento di Patologia Umana dell''Adulto e dell'Età Evolutiva, Policlinico G. Martino, University of Messina, Messina, Italy
- C. Elena
- 0UOC Ematologia 1, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- A. R. Scortechini
- 1Division of Hematology, Department of Molecular and Clinical Sciences, Polytechnic University of Marche, Ancona, Italy
- A. Tafuri
- 2Division of Hematology, Azienda Ospedaliera Universitaria Sant'Andrea, Rome, Italy
- R. Latagliata
- 3Division of Hematology, Belcolle Hospital, Viterbo, Italy
- G. Caocci
- 4Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy
- M. Bocchia
- 5Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy
- S. Galimberti
- 6Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- L. Luciano
- 7Division of Hematology, Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
- C. Fava
- 8Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
- R. Foà
- 6Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy
- G. Saglio
- 8Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
- G. Rosti
- 9Scientific Direction, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
- M. Breccia
- 6Division of Hematology, Department of Precision and Translational, Policlinico Umberto 1, Sapienza University, Rome, Italy
- DOI
- https://doi.org/10.3389/fphar.2023.1154377
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
- chronic myeloid leukemia
- tyrosine kinase inhibitors
- treatment-free remission
- low dose
- resistance
- outcome
