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1487 Analysis of Early Events during the First Year of Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase - Chronic Myeloid Leukemia: A “Campus CML” Study

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Adults, Clinical Research, Elderly, Clinically Relevant, Real World Evidence, Therapies, Young Adults, Study Population, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Saturday, December 11, 2021, 5:30 PM-7:30 PM

Mario Tiribelli, MD1*, Isabella Capodanno, MD2*, Maria Cristina Miggiano, MD3*, Cristina Bucelli, MD4*, Francesco Cavazzini, MD5*, Sabrina Leonetti Crescenzi, MD6*, Sabina Russo, MD7*, Emilia Scalzulli, MD8*, Andrea Bernardelli9*, Luigiana Luciano, MD10, Olga Mulas11*, Giuseppina Loglisci, MD12*, Chiara Elena, MD13*, Umberto Pizzano, MD14*, Immacolata Attolico, MD15*, Gianni Binotto, MD16*, Elena Crisà, MD17*, Paolo Sportoletti, MD18*, Ambra Di Veroli, MD19*, Anna Rita Scortechini, MD20*, Annapaola Leporace, MD21*, Maria Basile, MD22*, Monica Crugnola, MD23*, Fabio Stagno, MD, PhD24, Pamela Murgano, MD25*, Davide Rapezzi, MD26*, Alessandra Malato, MD, PhD27*, Michele Pizzuti, MD28*, Debora Luzi29*, Malgorzata Monika Trawinska, MD30*, Alessandra Iurlo, MD, PhD4*, Monica Bocchia31*, Carmen Fava, M.D.32, Giovanni Caocci, MD33, Massimiliano Bonifacio, MD34*, Giuseppe Nicola Saglio, MD, PhD35, Giorgina Specchia, MD36, Massimo Breccia, MD37* and Roberto Latagliata19*

1Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
2Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
3Hematology Department, San Bortolo Hospital, Azienda ULSS8 "Berica" di Vicenza, Vicenza, Italy
4Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
5Division of Hematology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy
6Hematology Unit, San Giovanni Hospital, Rome, Italy
7Division of Hematology, Policlinico “G. Martino”, University of Messina, Messina, Italy
8Hematology, Department of Translational and Precision Medicine, Policlinico Umberto I, Sapienza University, Rome, Italy
9Hematology, University of Verona, Verona, Italy
10Hematology Unit, Federico II University of Naples, Napoli, Italy
11Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
12Hematology Unit, Vito Fazzi Hospital, Lecce, Italy
13Department of Hematology Oncology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
14Hematology, University of Udine, Udine, Italy
15Hematology and Stem Cell Transplantation Unit, AOUC Policlinico, Bari, Italy
16Department of Medicine, Hematology and Clinical Immunology, Padua School of Medicine, Padua, Italy
17Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale Amedeo Avogadro, AOU Maggiore della Carità, Novara, Italy
18Department of Medicine, Division of Hematology and Clinical Immunology, University of Perugia, Perugia, Italy
19Hematology, Belcolle Hospital, Viterbo, Italy
20Division of Hematology, Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona, Ancona, Italy
21Hematology Unit, Azienda Ospedaliero Universitaria Sant' Andrea, Rome, Italy
22Hematology, Giuseppe Moscati Hospital, Taranto, Italy
23Hematology and BMT Center, Department of Medicine and Surgery, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
24Chair and Hematology Section, Ferrarotto Hospital, Catania, Italy
25Division of Hematology, S. Elia Hospital, Caltanissetta, Italy
26S.C. Ematologia, ASO S. Croce e Carle, Cuneo, Italy
27Department of Hematology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
28Ematologia, Azieda Ospedaliera S. Carlo, Potenza, Italy
29Hematology, Azienda Ospedaliera - S. Maria Terni, Terni, ITA
30Department of Hematology S. Eugenio Hospital, Rome, Italy
31Hematology, Hematology Unit, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
32Hematology Division, Ospedale Mauriziano, University of Turin, Torino, Italy
33Department of Medical Sciences and Public Health, University of Cagliari, Businco Hospital, Cagliari, Italy
34Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
35Divisione Universitaria di Ematologia e Terapie Cellulari, A.O. Ordine Mauriziano, Turin, Italy
36Hematology Section, Department of Emergency and Transplantation - GIMEMA WP CML, University of Bari Aldo Moro, Bari, Italy
37Division of Hematology, Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University, Rome, Italy

Background Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the first months of therapy are crucial, as optimal response is defined as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st year.

Methods To evaluate achievement of early molecular response (MR) and incidence of events leading to a TKI change during the 1st year of therapy, we retrospectively studied 1650 CP-CML patients diagnosed from 2012 and 2019 at 31 Hematology Centres and treated with frontline imatinib (IM) or second-generation (2G) TKIs dasatinib or nilotinib. Optimal MR at 3, 6 and 12 mo. were assessed according to 2020 ELN recommendations.

Results Frontline TKI was IM in 926 (56.1%) and 2G-TKIs in 724 (43.9%) cases: the main clinical features at diagnosis of the entire cohort and according to frontline treatment is reported in the Table 1. Commonest comorbidities were arterial hypertension (38.7%), previous neoplasm (13.6%), diabetes (11.3%), peripheral vascular diseases (7.8%), COPD (7.5%) and ischemic heart disease (6.8%). IM-treated patients were older (p<0.001), with higher ELTS score (int/high 47.6% vs 35.6%, p<0.001) and more comorbidities (p<0.005 for all diseases).

Optimal MR was achieved at 3 mo. by 1186/1430 (82.9%), at 6 mo. by 1025/1352 (75.8%) and at 12 mo. by 826/1264 patients (65.3%), respectively.

Total number of patients discontinuing TKI in the 1st year was 321/1650 (19.4%), being higher with IM (237/926, 25.5%) than 2G-TKIs (84/724, 11.6%) (p<0.001). Main causes were primary resistance (8.7%, 12.3% IM vs 4.2% 2G-TKIs, p<0.001), extra-hematologic toxicity (6.4%, 8.2% IM vs 4.2% 2G-TKIs, p>0.001), hematologic toxicity (1.7%, 2.0% IM vs 1.4% 2G-TKIs, p=0.25) and progression (1.0%, 1.2% IM vs 0.8% 2G-TKIs, p=0.56). Cumulative incidence of discontinuation at 3, 6 and 12 mo. were 5.6%, 10.7% and 19.3%, respectively; values for IM and 2G-TKIs at the three timepoints were 8.1%, 15.0%, 25.5% and 2.5%, 5.3%, 11.5% (p<0.001) (Fig. 1).

Conclusions This real-world study on over 1600 CML patients shows that almost 20% discontinue frontline TKI during the 1st year, mostly for primary resistance or toxicity. Discontinuation rates are higher with IM compared to 2G-TKIs, mostly at 3 mo. and are probably due to a lower attainment of early MR. The impact of older age, higher risks and heavier burden of comorbidities in IM patients should be considered and need deeper investigation.

Disclosures: Elena: GILEAD: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; CELGENE: Other: funding for meeting participation. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: InCyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Iurlo: Pfizer: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Novartis: Honoraria. Latagliata: Novartis: Honoraria; Pfizer: Honoraria; BMS Cellgene: Honoraria.

*signifies non-member of ASH