Michele Malagola1, Alessandra Iurlo2, Elisabetta Abruzzese3, Massimiliano Bonifacio4, Fabio Stagno5, Gianni Binotto6, Mariella D'Adda7, Monia Lunghi8, Monica Crugnola9, Maria Luisa Ferrari10, Francesca Lunghi11, Fausto Castagnetti12, Gianantonio Rosti13, Roberto M Lemoli14, Rosaria Sancetta15, Maria Rosaria Coppi16, Maria Teresa Corsetti17, Giovanna Rege Cambrin18, Atelda Romano19, Mario Tiribelli20, Antonella Russo Rossi21, Sabina Russo22, Lara Aprile23, Monica Bocchia24, Lisa Gandolfi1, Mirko Farina1, Simona Bernardi1,25, Nicola Polverelli1, Aldo M Roccaro26, Antonio De Vivo12, Michele Baccarani27, Domenico Russo1. 1. Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili, Brescia, Italy. 2. Hematology Division, Foundation IRCCS Ca, Granda Ospedale Maggiore Policlinico, Milan, Italy. 3. Division of Hematology, S. Eugenio Hospital, ASL ROMA2, Tor Vergata University, Roma, Italy. 4. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy. 5. Department of Hematology, University of Catania, Catania, Italy. 6. Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padua, Italy. 7. Division of Hematology, ASST-Spedali Civili di Brescia, Brescia, Italy. 8. Division of Hematology, Department of Translation Medicine, University of Eastern Piedmont, Novara, Italy. 9. Hematology Unit and BMT Center Azienda Ospedaliero Universitaria Parma, Parma, Italy. 10. Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. 11. Hematology and Bone Marrow Transplantation (BMT) Unit, San Raffaele Scientific Institute, Milan, Italy. 12. Hematology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy. 13. IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy. 14. Clinic of Hematology, University of Genoa, Ospedale Policlinico S. Martino, IRCCS, Genoa, Italy. 15. Hematology Unit, Dell'Angelo Hospital, Venezia-Mestre, Italy. 16. Haematology and BMT Unit "Antonio Perrino" Hospital, Brindisi, Italy. 17. Hematology Division, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy. 18. Medicina Interna a Indirizzo Ematologico, Ospedale San Luigi, Orbassano, Italy. 19. IRCCS Regina Elena National Cancer Institute-Rome, Roma, Italy. 20. Division of Hematology and BMT, Department of Medical and Morphological Researches, University of Udine, Udine, Italy. 21. Hematology and Transplants Unit, University of Bari, Bari, Italy. 22. Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età Evolutiva, Policlinico G Martino, University of Messina, Messina, Italy. 23. SC Ematologia, Ospedale S.G.Moscati, Taranto, Italy. 24. Hematology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy. 25. CREA Laboratory (Hematological-Research AIL Centre), ASST-Spedali Civili Brescia, Brescia, Italy. 26. Clinical Research Development and Phase I Unit, ASST-Spedali Civili Brescia, Brescia, Italy. 27. University of Bologna, Bologna, Italy.
Abstract
BACKGROUND: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. METHODS: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL). RESULTS: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). CONCLUSIONS: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.
BACKGROUND: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. METHODS: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL). RESULTS: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). CONCLUSIONS: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.
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Authors: S Wheelwright; A-S Darlington; D Fitzsimmons; P Fayers; J I Arraras; F Bonnetain; E Brain; A Bredart; W-C Chie; J Giesinger; E Hammerlid; S J O'Connor; S Oerlemans; A Pallis; M Reed; N Singhal; V Vassiliou; T Young; C Johnson Journal: Br J Cancer Date: 2013-07-18 Impact factor: 7.640
Authors: A Hochhaus; M Baccarani; R T Silver; C Schiffer; J F Apperley; F Cervantes; R E Clark; J E Cortes; M W Deininger; F Guilhot; H Hjorth-Hansen; T P Hughes; J J W M Janssen; H M Kantarjian; D W Kim; R A Larson; J H Lipton; F X Mahon; J Mayer; F Nicolini; D Niederwieser; F Pane; J P Radich; D Rea; J Richter; G Rosti; P Rousselot; G Saglio; S Saußele; S Soverini; J L Steegmann; A Turkina; A Zaritskey; R Hehlmann Journal: Leukemia Date: 2020-03-03 Impact factor: 11.528