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50 Predictive Factors for Overall Survival in Chronic Myeloid Leukemia Patients: An Analysis By the Gimema Cml Italian StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 632. Chronic Myeloid Leukemia: Therapy— Building The Future CML
Hematology Disease Topics & Pathways:
Diseases, CML, Myeloid Malignancies, Clinically relevant
Saturday, December 5, 2020: 8:45 AM

Giorgina Specchia, MD1, Patrizia Pregno2*, Massimo Breccia, MD3*, Chiara Monagheddu4*, Fausto Castagnetti, MD, PhD5,6, Massimiliano Bonifacio, MD7*, Mario Tiribelli, MD8*, Fabio Stagno, MD, PhD9, Giovanni Caocci, MD10, Bruno Martino, MD11*, Luigiana Luciano, MD12, Michele Pizzuti, MD13*, Antonella Gozzini, MD14*, Anna Rita Scortechini, MD15*, Francesco Albano16*, Micaela Bergamaschi, MD17*, Isabella Capodanno, MD18*, Andrea Patriarca, MD19*, Carmen Fava20, Giovanna Rege Cambrin, MD, PhD21*, Federica Sorà, MD22*, Sara Galimberti, MD, PhD23*, Monica Bocchia24*, Gianni Binotto, MD25*, Giovanni Reddiconto26*, Attilio Guarini, MD27*, Alessandro Maggi28*, Grazia Sanpaolo, MD29*, Maria Stella De Candia30*, Valentina Giai, MD, PhD31, Elisabetta Abruzzese, MD 32, Maria Cristina Miggiano, MD33*, Franca Falzetti, MD34*, Gaetano La Barba35*, Giuseppe Pietrantuono36*, Anna Guella, MD37*, Luciano Levato, MD38*, Olga Mulas39*, Fabio Saccona40*, Gianantonio Rosti, MD41*, Pellegrino Musto, MD42, Francesco Di Raimondo, MD43, Fabrizio Pane, MD44, Robin Foà, MD45, Michele Baccarani, MD46, Giovannino Ciccone4* and Giuseppe Saglio, MD, PhD47

1Hematology Section, Department of Emergency and Transplantation - GIMEMA WP CML, University of Bari Aldo Moro, Bari, Italy
2Hematology Unit, Az Ospedaliero Universitaria Città' della Salute e della Scienza, Torino, Italy
3Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy
4Unit of Clinical Epidemiology and CPO, Città della Salute Hospital and University, Torino, Italy
5Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
6Institute of Hematology "L. and A. Seràgnoli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, "S. Orsola-Malpighi" Hospital, Bologna, Italy
7Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
8Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
9Chair and Hematology Section, Ferrarotto Hospital, Catania, Italy
10Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy
11Hematology Unit, A.O. Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
12Hematology Unit, Federico II University of Naples, Napoli, Italy
13Ematologia, Azieda Ospedaliera S. Carlo, Potenza, Italy
14Hematology Unit, AOU Careggi, University of Florence, Florence, ITA
15Division of Hematology, Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona, Ancona, Italy
16University of Bari, Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, Bari, Italy
17Clinical Hematology Unit, IRCCS AOU S.Martino-IST, Genova, Italy
18Hematology Unit, Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy
19Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
20Hematology Division, Ospedale Mauriziano, University of Turin, Torino, Italy
21Division of Internal Medicine - Hematology, AUO San Luigi, Orbassano, Italy
22Institute of Hematology, Università Cattolica del Sacro Cuore - Policlinico A. Gemelli, ROMA, Italy
23Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy
24Hematology, University of Siena, Siena, Italy
25Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
26U.O.Hematology Hospital V.Fazzi - Lecce Italy, Lecce, Italy
27Haematology Unit, Istituto Tumori Giovanni Paolo II I.R.C.C.S. Ospedale Oncologico, Bari, Italy
28Hematology, " Giuseppe Moscati" Hospital, Taranto, Italy
29Division of Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
30Hematology Unit, Ospedale Perrino, Brindisi, Italy
31Università Degli Studi Di Torino, Turin, Turin, Italy
32Hemoglobinopathies Unit, Hematology Department, S. Eugenio Hospital (ASL Roma 2), Tor Vergata University, Rome Italy, Rome, Italy
33Hematology Department, San Bortolo Hospital, Vicenza, Italy
34Institute of Hematology, Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
35Department of Hematology, "Spirito Santo" Hospital, Pescara, ITA
36IRCCS Centro Oncologico Della Basilicata, Rionero In Vulture, ITA
37Ematology section, Ematology section,U.O. Medicina II,Ospedale Santa Chiara, trento, Italy
38Hematology Unit, A. Pugliese Hospital, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy
39Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
40SCDU Epidemiologia dei Tumori-CPO Piemonte, Az Osp Citta della salute e della Scienza, Turin, Italy
41Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Institute of Hematology "L. and A. Seràgnoli", S.Orsola-Malpighi University Hospital, Bologna, Italy
42Hematology and Stem cell Transplantation Unit - Department of Emergency and Organ Transplantation (D.E.T.O.) - University of Bari, Bari, Italy
43Division of Hematology, A.O.U. "Policlinico-Vittorio Emanuele", University of Catania, Catania, Italy
44Federico II University of Naples, Hematology Department, Naples, Italy
45Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy
46Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna-GIMEMA WP CML, Institute of Hematology and Medical Oncology "L. & A. Seràgnoli", Bologna, Italy
47Divisione Universitaria di Ematologia e Terapie Cellulari, A.O. Ordine Mauriziano, Turin, Italy

Introduction

Tyrosine kinase inhibitors (TKIs) have dramatically changed the outcome of chronic phase chronic myeloid leukemia patients (CP-CML),improving the long-term outcome; indeed, life expectancy is now very close to that of age matched individuals in the general population. Imatinib (IMA) the first generation TKI, increased the overall survival(OS)by more than 80%. Second-generation TKIs, (2gen TKIs) used in first line dasatinib and nilotinib, induced faster molecular responses, rapidly reducing the disease burden, but did not change the OS of CP-CML newly diagnosed patients. Most of the available data reported were extrapolated from sponsored clinical trials. The aim of this analysis is to detail and analyze the prognostic features influencing the OS in a large Italian CML cohort of patients prospectively enrolled in the GIMEMA CML Italian study.

Methods

Relevant clinical, demographic, biological and treatment-related information were web-based collected during a multicenter,observational Italian study that enrolled consecutive patients in each disease phase, at 68 Italian hematologic centers belonging to the GIMEMA network from January 2013 to June 2020. We analyzed prognostic factors influencing the OS by Kaplan Meier method and Cox multivariable models.

Results

A cohort of 1206 patients was prospectively analyzed, 608 of them received frontline IMA and 598 2genTKIs. Median age in the IMA cohort was 69 years (range 58-77) vs 52 years in the 2genTKIs cohort (range 41-63). The male/female ratio was 1.7 in the IMA group and 1.35 in the 2genTKIs cohort. Ninety-eight percent of patients were in CP. Results of molecular analysis of the BCR-ABL transcript at baseline showed: b2a2 in 33.1 % of patients and b3a2 in 59.9%, while an atypical transcript was found in 7%. The cytogenetic analysis at baseline showed major and minor additional aberrations in 5.7% and 1.6% of patients respectively. In the IMA cohort,according to the Sokal score, 27.7%, 57.3% and 15% of patients were stratified as low, intermediate and high risk, whereas according to the ELTS score 51.3%, 35.5% and 13.3%, of patients were classified as low, intermediate and high risk. In the 2genTKIs cohort, according to the Sokal score, 44.8%, 34.5% and 20.8%, were low, intermediate and high risk, respectively, whereas according to the ELTS score, 66.9%, 22% and 11% were assigned to the respective risk groups.The Charlson comorbidity index in the IMA cohort was 2-3 and 4-5 in 74% and 26% of patients respectively; in the 2genTKIs cohort the score was 2-3 in 89% and 4-5 only in 10% of patients. Overall, median follow-up of the whole population was 24.7 months (range 13.3-39.3).Seventy-three patients (6.1%) in the overall population died, the majority of them in the IMA cohort: 56 patients (9.2%), at median age of 80.5 years,11/608 (1.8%) due to CML-related causes. Conversely,in the 2genTKIs cohort only 17 patients (2.8%) died, at a median age of 62 years, 10/598 (1.7%) for CML-related causes. Estimated 60-months OS of the overall population was 86.4% (95% CI 81.3-90.2): 75.8% (95% CI 64.5-84) in the IMA cohort and 93.8% (95% CI 87.5-97) in the 2genTKIs group (p<0.0001). The ELTS score provides a better stratification of 60 months OS both in the IMA (OS 60-months 91.4%, 65.2%, 48.7% in low, intermediate and high risk, p<0.0001) (Fig.1a) and the 2genTKIs subgroups (OS 60-months OS 95.4%, 92%, 87.9% in low, intermediate and high risk, p=0.0013)(Fig.1b). An adjusted Cox model on the entire population showed that prognostic factors influencing OS are: ELTS score (high risk vs low HR= 5.2, 95%CI 2.7-10.03, p<0.0001),the type of TKI (2genTKIs vs IMA HR= 0.46; 95% CI 0.24-0.87, p=0.018), age (HR=1.03 per year, 95%CI 1.00-1.05, p=0.025) and the Charlson index (4-5 vs 2-3, HR= 1.75, 95%CI 1.43-2.1, p<0.0001).

Conclusions

In this first analysis of our study different clinical behaviors were observed among Italian hematologists, who prevalently prescribed IMA to older patients,with more comorbidities, as compared to 2genTKIs.These differences explain a better OS for patients treated with 2genTKIs vs IMA, however, the risk of death for CML related causes is quite similar between the two groups, all the differences being attributable to other causes of death.Prognostic baseline features associated to an increased OS confirmed that, in addition to age, the ELTS score and the comorbidities are the main clinical factors that independently influence the long-term OS

Disclosures: Pregno: Incyte-Italy,: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Novartis-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Pfizer-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports. Breccia: Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy. Castagnetti: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Galimberti: Novartis: Speakers Bureau; Incyte: Honoraria. Bocchia: CELGENE: Honoraria; Incyte: Honoraria. Abruzzese: Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levato: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rosti: Pfizer: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Di Raimondo: GILEAD, Incyte: Research Funding; Amgen, Takeda, Novartis: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Pane: Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Foà: Incyte: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Saglio: Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Roche: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

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