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Malagola, M.1; Efficace, F.2; Polverelli, N.1; Cottone, F.2; Abruzzese, E.3; Iurlo, A.4; Bucelli, C.4; Stagno, F.5; Bonifacio, M.6; D'Adda, M.7; Lunghi, M.8; Crugnola, M.9; Lunghi, F.10; Castagnetti, F.11; Rosti, G.11; Ferrari, M. L.12; Bergamaschi, M.13; Binotto, G.14; Sancetta, R.15; Coppi, M. R.16; Giai, V.17; Cambrin, Rege G.18; Romano, A.19; Tiribelli, M.20; Russo, S.21; Aprile, L.22; Falcone, A. P.23; Rupoli, S.24; Rossi, Russo A.25; Usala, E.26; Martino, B.27; Gandolfi, L.1; Bernardi, S.1; Zanaglio, C.1; Farina, M.1; Baccarani, M.11; Russo, D.1

doi: 10.1097/01.HS9.0000561808.14876.94
Simultaneous Sessions III: Future implications of management in CML

1Chair of Hematology, Dept of Clinical and Experimental Sciences,University of Brescia, ASST Spedali Civili di Brescia, Brescia

2Health Outcomes Research Unit, Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), GIMEMA Data Center and Health Outcomes Research Unit

3Hematology, S Eugenio Hospital,, Tor Vergata University, Rome

4Hematology Division, Foundation IRCCS Ca' Granda - Maggiore Policlinico, Milano

5Department of Hematology, University of Catania, Catania

6Department of Medicine, Section of Hematology, University of Verona, Verona

7Division of Hematology, ASST-Spedali Civili di Brescia, Brescia

8Division of Hematology, Department of Translation Medicine, University of Eastern Piedmont, Novara

9Hematology Unit, Maggiore Hospital University of Parma, Parma

10Hematology and Bone Marrow Transplantation (BMT) Unit, San Raffaele Scientific Institute, Milano

11Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology “L. & A. Seràgnoli”, University of Bologna, Bologna

12Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo

13Clinical Hematology, Ospedale Policlinico S. Martino, Istituto di Ricovero e Cura a Carattere Scientifico, Genova

14Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova

15Hematology Unit, Dell'Angelo Hospital, Venezia Mestre

16Haematology and BMT Unit “Antonio Perrino” Hospital, Brindisi

17Hematology Division, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria

18Hematology Division, Ospedale Mauriziano, Torino

19Istituto Nazionale Tumori Regina Elena - IFO, Roma

20Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine

21Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età Evolutiva, Policlinico G Martino, University of Messina, Messina

22Hematology Unit, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena

23Hematology Unit, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo

24Hematology Clinical Unit, Ancona Hospital, Ancona

25Hematology and Transplants Unit, University of Bari, Bari

26Hematology Unit, Ospedale Oncologico A. Businco, Cagliari

27Hematology Unit Bianchi Melacrino Morelli Hospital, Reggio Calabria, Italy

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The therapeutic strategy of CML in the TKIs era aims to improve the management of the disease and possibly also patients' quality of life (QoL).

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In July 2015, we started a prospective multicentric randomized trial with the aim to validate the policy of the intermittent de-escalation treatment and to examine the impact of this strategy on QoL.

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To this purpose, CML patients older than 60 years in stable (≥2 years) MR3.0 or MR4.0 molecular response were randomized to receive a FIXED intermittent TKIs regimen (one month ON and one month OFF) (Russo D, Blood 2013; Russo D, BCJ 2015), versus a PROGRESSIVE intermittent TKIs regimen (one month ON and one month OFF for the 1st year; one month ON and two months OFF for the 2nd year; one month ON and three months OFF from the 3rd year) (OPTkIMA study, NCT02326311). Molecular monitoring was performed according to the 2015 ELN guidelines (Baccarani M, Blood2013). In case of confirmed MR3.0 (MMR) loss, patients were planned to exit the study and to resume TKIs daily. QoL was evaluated at baseline, every three months during the first year and regularly thereafter, using the well validated EORTC QLQ-C30 and its CML module (EORTC QLQ-CML24) as well as the EORTC Elderly Module (EORTC QLQ-ELD14). For the purpose of this preliminary QoL analysis we only considered changes from baseline up to 12 months, that is when both patient groups receive the same treatment schedule (one month ON and one month OFF).

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This first interim report, have been focused on the patients who, by intention to treat, have completed the first year of the study. Up to December 2018, 186 patients have been enrolled by 26 Italian Hematological Centers and 166/186 patients (89%) completed the first year of OPTkIMA study. The median age was 71 years (range 60-89) and 66% of the patients were belonging to the Sokal intermediate/high risk goup. 129/166 (77%) patients were receiving imatinib (IMA). Overall, 89/166 (54%) and 77/166 (46%) patients have been randomized in the FIXED and PROGRESSIVE arm, respectively. 46/76 patients (61%) randomly assigned to the PROGRESSIVE arm have entered the second year of therapy. 47/166 patients (28%) went out of the study during the first year (Table 1). 39/166 cases (23%) lost MR3.0. Thus the probability of loosing the MR3.0 while on OPTkIMA was 19% at one year (Figure 1). All the 39 patients resumed TKIs continuously and all obtained at least the MR3.0 response, within 6 months. The intermittent treatment was well tolerated, with 7 serious adverse events, none of which treatment-related. None of the patients experienced the TKI withdrawn syndrome. QoL analysis was based on 166 patients with currently available QoL data. The top three most prevalent baseline symptoms (EORTC QLQ-C30) were fatigue (80%), pain (51%) and sleep disturbance (48%). With regard to QoL disease-specific domains (EORTC QLQ-CML24), no statistically significant changes were noted during the first year of treatment. Further QoL analyses are currently ongoing.



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According to this first interim report, we found that a policy of intermittent TKIs administration in elderly patients is safe and well tolerated. After the 1st year, 28/166 patients (23%) lost MR3.0 and all of them re-gained the major molecular response within 6 months from resumption of continuous treatment. Thus, the probability of MR3.0 loss while on OPTkIMA at 1 year was 19%, comparable to the 20% of the previously published INTERIM trial.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.