-Author name in bold denotes the presenting author
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2156 Low Cholesterol, Low-Density Lipoprotein (LDL) and Triglycerides Plasma Levels Are Associated with Lower Risk of Arterial Occlusive Events in Chronic Myeloid Leukemia Patients Treated with NilotinibClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II
Hematology Disease Topics & Pathways:
Therapies, Adverse Events, Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Giovanni Caocci, MD1, Olga Mulas2*, Isabella Capodanno, MD3*, Mario Annunziata, MD4*, Elisabetta Abruzzese, MD 5, Sara Galimberti, MD, PhD6*, Mario Tiribelli, MD7*, Luigiana Luciano, MD8, Bruno Martino, MD9*, Fausto Castagnetti, MD, PhD10, Gianni Binotto, MD11*, Patrizia Pregno12*, Fabio Stagno, MD, PhD13, Monica Bocchia14*, Francesco Albano15*, Debora Luzi16*, Claudio Fozza, MD17*, Massimiliano Bonifacio, MD18*, Chiara Elena, MD19*, Antonella Gozzini, MD20*, Maria Pina Simula21*, Malgorzata Monika Trawinska, MD22*, Claudia Baratè, MD6*, Rossella Stella, MD7*, Fiorenza De Gregorio, MD23*, Gabriele Gugliotta, MD, PhD10, Francesca Pirillo24*, Daniele Cattaneo25*, Anna Sicuranza, PhD26*, Imma Attolico, MD27*, Luigi Scaffidi, MD18*, Emilia Scalzulli, MD28*, Alessandra Iurlo, MD, PhD29*, Robin Foà, MD30, Massimo Breccia, MD31* and Giorgio La Nasa, MD32*

1Ematologia-Centro Trapianti Midollo Osseo, Ospedale Businco, Dipartimento di Scienze mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy
2Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
3Hematology Department, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
4Hematology Unit, Cardarelli Hospital, Naples, Italy
5Hemoglobinopathies Unit, Hematology Department, S. Eugenio Hospital (ASL Roma 2), Tor Vergata University, Rome Italy, Rome, Italy
6Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy
7Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
8Hematology Unit, Federico II University of Naples, Napoli, Italy
9Division of Hematology, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
10Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
11Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
12AZ OSP CITTA' DELLA SALUTE E SCIENZA TORINO, University of Torino, TORINO, Italy
13Hematology Section and BMT Unit, Rodolico Hospital, AOU Policlinico - V. Emanuele, Catania, Catania, Italy
14Hematology, University of Siena, Siena, Italy
15Hematology and Stem cell Transplantation Unit - Department of Emergency and Organ Transplantation (D.E.T.O.) - University of Bari, Bari, Italy
16Hematology, Azienda Ospedaliera - S. Mariai Terni, Terni, ITA
17Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
18Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
19Department of Hematology Oncology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
20Hematology Unit, AOU Careggi, University of Florence, Florence, ITA
21Hematology, Businco Hospital, Cagliari, ITA
22ASL Roma2, Department of Hematology S. Eugenio Hospital, Rome, Italy, Rome, Italy
23Hematology - Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
24Hematology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy
25FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO, MILANO, ITA
26Hematology, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy
27Haematology, University of Bari, Potenza, Italy
28Department of Cellular Biotechnologies and Hematology, University "Sapienza", Rome, Italy
29Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
30Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Rome, Italy
31Department of Translational and Precision Medicine, Sapienza University, Roma, Italy
32Hematology, Hospital Businco, Department of Medical Sciences, University of Cagliari, Cagliari, Italy

Introduction. New guidelines for the management of dyslipidemia and lipid modification in order to reduce the risk of cardiovascular (CV) events have been recently published by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). New recommendations regarding the target value of plasma lipids in very high and high CV risk patients have been provided, in addition to an estimate of the CV risk with a new Systematic Coronary Risk Evaluation (SCORE) chart. Few data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib, and the association with arterial occlusive events (AOEs). We therefore analyzed a large real-life cohort of Italian patients with CML treated with nilotinib outside of clinical trials and evaluated the association between AOEs and plasma lipoproteins levels; moreover, we estimated the prognostic value of the new SCORE chart to predict AOEs. The secondary endpoint was to report the management of dyslipidemia in the clinical practice.

Methods. We identified 233 adult patients with CML who were treated in 20 Italian centers with nilotinib. All patients were stratified into low to moderate (SCORE ≤ 5%) or high to very high (SCORE risk >5%) CV risk, according to the new version of the SCORE 2019. We recorded concentration levels of cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides at diagnosis of CML, before starting ponatinib and therefore after 3, 6 and 12 months of treatment. All AOEs (cerebrovascular, peripheral vascular and CV events excluding hypertension) were considered.

Results. The median age was 50 years (range 20-88) and the Sokal score was intermediate-high in 45.5% of patients. The median follow-up was 5 years (range 3.4-10.5). Nilotinib was administered as first line of therapy in (72%) of cases or second or subsequent lines of treatment for inefficacy (20.9%) or intolerance (7.1%). At baseline, nilotinib was administered at the following doses: 800 mg/day in 9.3% of patients, 600 mg/day in 87% of patients, 400 mg/day in 3.1% of patients and 300mg in 0.6% of patients, respectively. The median time of drug exposure was 60 months (range 2-155). The 48-month cumulative incidence rate of AOEs was 14.1±2.7%.

Patients with cholesterol plasma levels > 200 mg/dL and LDL >70 mg/dL at baseline and 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (24.5±7.3% vs 11±2.7%, P=0.02 and 22.3±4.9% vs 5.9±2.6, P=0.003, respectively) Figure 1. Patients with triglycerides levels > 200 mg/dL 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (56±20.5% vs 13.3±2.7%, P=0.011)

Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (32.8.1±9% vs. 9±1%±2.6%, p=0.001). In multivariate analysis, statistical significance of cholesterol plasma levels > 200 mg/dL and LDL >70 mg/dL after 3 months and high-very-high SCORE was maintained (P=0.018, HR=3.4, 95% CI=1.2-9.4 and P=0.004, HR=3.5, 95% CI=1.5-8.2, respectively). Overall, 46 patients (20.5%) presented dyslipidemia at CML diagnosis and 65 (29%) at the start of treatment with nilotinib. Despite dyslipidemia, only 6 patients were taking statins during the treatment with nilotinib and only 5 started it after 3 months of nilotinib: 3 patients were treated with rosuvastatin and 2 with pravastatin.

Conclusions. Our findings suggest that a proper control of dyslipidemia, keeping cholesterol and triglycerides plasma levels ≤ 200 mg/dL and LDL ≤70 mg/dL is associated with reduced risk of AOEs in CML patients treated with nilotinib. An under estimation of the clinical importance of elevated plasma lipids as a risk factor for AOEs events represents a possible issue in the real-life.

Disclosures: Abruzzese: Pfizer: 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; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria. Galimberti: Incyte: Honoraria; Novartis: Speakers Bureau. Castagnetti: Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. 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. Bocchia: CELGENE: Honoraria; Incyte: Honoraria. Gugliotta: Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Foà: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH