-Author name in bold denotes the presenting author
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1241 Safety and Efficacy Profile of Asciminib As Treatment in Chronic Myeloid Leukemia Patients after Several Tyrosine-Kinase Inhibitors FailureClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster I
Hematology Disease Topics & Pathways:
Biological, CML, Diseases, Therapies, Adverse Events, Clinically relevant, Myeloid Malignancies, TKI
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Alejandro Luna, MD1*, Natalia Estrada2*, Concepcion Boque, MD. PhD3*, Blanca Xicoy, MD4*, Pilar Giraldo, PhD5, Anna Angona6*, Alberto Alvarez-Larrán, MD, PhD7*, Fermin Sanchez-Guijo, MD, PhD8*, María José Ramírez9*, Juan M. Alonso-Domínguez10*, Elvira Mora11*, Patricia Vélez, MD12*, Ana Rosell13*, Mercedes Colorado Araujo14*, Beatriz Cuevas, MD15*, Miguel Sagüés3*, Montserrat Cortes16*, Manuel Perez Encinas, MD17*, Luis Felipe Casado Montero, MD18, Melania Moreno Vega19*, Luis Serrano20*, Valle Gomez21*, Carmen Garcia-Hernandez, MD22*, Sunil Lakhwani Lakhwani23*, Antonio Paz Coll24*, Raquel de Paz, MD25*, Sara Suarez-Varela26*, Andrés Fernandez-Ruiz3*, Raul Perez Lopez27*, Almudena Ortiz-Fernández28*, Antonio Jiménez-Velasco, MD29* and Valentín Garcia-Gutiérrez, MD, PhD1

1Hematology, Hospital Universitario Ramón y Cajal, Madrid, Spain
2Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Badalona, Spain
3Institut Catala d'Oncologia - L'Hospitalet de Llobregat, L'Hospitalet de Llobregat, Spain
4Hematology Department, Institut Català d'Oncologia-Hospital Germans Trias i Pujol; Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
5Hospital Quiron Zaragoza, Zaragoza, Spain
6Hematology, Institut Català d'Oncologia - Girona, Girona, Spain
7Hematology Department, Hospital Clínic, Barcelona, Spain
8Hematology Department, IBSAL-Hospital Universitario de Salamanca, CIC and CIBERONC, University of Salamanca, Salamanca, Spain
9Hematology Department, Hospital de Jerez de la Frontera, Jerez, Spain
10Hospital Universitario Fundación Jiménez Díaz, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), UAM, Madrid, Spain
11Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
12Hospital Mutua Terrassa, Terrassa, Spain
13Hematology, Hospital Virgen de la Victoria, Malaga, Spain
14Hospital U. Marqués de Valdecilla, Servicio de Hematología-Hemoterapia, Santander, Spain
15Hematology, Hospital Universitario de Burgos, BURGOS, ESP
16Hospital General de Granollers, Barcelona, Spain
17Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
18Hospital Virgen de la Salud, Toledo, Madrid, Spain
19Hospital Doctor José Molina Orosa de Lanzarote, Arrecife, Spain
20Hospital General de Castellón, Castellón, Spain
21Hospital Universitario La Princesa, Madrid, ESP
22Hospital General de Alicante, Alicante, Spain
23Department of Hematology, Hospital Universitario de Canarias, La Laguna, La Laguna, Spain
24Hospital Universitario Puerto Real, Puerto Real, ESP
25Hematology Department, Hospital Universitario La Paz-Idipaz, Madrid, Spain
26Hospital de Jerez de la Frontera, Jerez de la Frontera, Spain
27Servicio de Hematología, Hospital Universitario Clínico Virgen de la Arrixaca, MURCIA, Spain
28Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
29Hospital Universitario Carlos Haya, Malaga, Spain

Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience.
The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program.

Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0).

Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects.

Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs.

Disclosures: Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

*signifies non-member of ASH