-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1708 Toxicity of Asciminib in Real Clinical Practice; Analysis of Side Effects and Cross-Intolerance with Tyrosine Kinase Inhibitors

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Non-Biological therapies, CML, Chronic Myeloid Malignancies, Diseases, Therapies, Adverse Events, Myeloid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Lucía Pérez-Lamas1*, Alejandro Luna, MD2*, Concepcion Boque, MD. PhD3*, María Alicia Senin, MD4*, Blanca Xicoy, MD5*, Pilar Giraldo, PhD6, Raul Perez Lopez, MD, PhD7*, Concepción Ruiz Nuño8*, Natalia De las Heras, MD9*, Elvira Mora Casterá, MD10*, Carmen Garcia-Hernandez, MD11*, Adrian Segura Diaz12*, Juan Luis Steegmann, Prof., MD.13*, Patricia Velez Tenza14*, Fermin Sanchez-Guijo, MD, PhD15*, Ana Maria Garcia-Noblejas Moya16*, Juan Antonio Juan Vera Goñi, MD17*, Melania Moreno Vega18*, Alberto Alvarez-Larran, MD, PhD19*, Montse Cortes, MD20*, Manuel Perez Encinas, MD21*, Luis Serrano22*, Anna Angona, MD23*, Ana Rosell24*, Sunil Lakhwani25*, Mercedes Colorado26*, Elena Ramila, MD27*, Carlos Cervero, MD28*, Beatriz Cuevas, MD, PhD29*, Lucia Villalon Blanco30*, Juan Carlos Hernandez Boluda, MD, PhD31*, Antonio Paz Coll32*, Valle Gómez García de Soria33*, Maria Jose Fernández34*, Luis Felipe Casado, MD35*, Juan Manuel Alonso-Dominguez36*, Maria Magdalena Anguita Arance37*, Patricia Carrascosa Mastell, MD38*, Araceli Salamanca Cuenca39*, Antonio Jiménez-Velasco, MD40*, María José Ramírez41*, Miguel López Esteban42*, Magdalena Sierra Pacho43*, Marta Santaliestra44*, Olga Alda Alvarez45*, Raquel de Paz, PhD46* and Valentín García Gutiérrez, PhD47

1Hematology department, Hospital Ramón y Cajal, Madrid, Spain
2Hematology, Hospital Universitario Ramón y Cajal, Madrid, Spain
3Institut Catala d'Oncologia - L'Hospitalet de Llobregat, L'Hospitalet de Llobregat, Spain
4Hospital Duran i Reynals, Institut Catalá dÓncologia, L´Hospitalet de LLobregat., ESP
5Hematology Department, Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain
6Hospital Quirónsalud Zaragoza, Zaragoza, Spain
7HU Virgen de la Arrixaca, Murcia, Spain
8Hospital Regional Universitario de Málaga, Málaga, Spain
9Department of Hematology, Hospital Universitario de Leon, Leon, Spain
10Dept. of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
11Hospital General de Alicante, Alicante, Spain
12Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, AE, ESP
13Hematology, Hospital La Princesa, Madrid, Spain
14Hospital Del Mar, Barcelona, Spain
15Hematology Department, Hospital Clínico Universitario de Salamanca (CAUSA/IBSAL), Salamanca, Spain
16Hospital Universitario La Princesa, Madrid, ESP
17Hospital Virgen Macarena, Sevilla, Spain
18Hospital Doctor José Molina Orosa de Lanzarote, Arrecife, Spain
19Hematology Department, Hospital Clínic, Barcelona, Spain
20HG de Granollers, Barcelona, Spain
21Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
22Hospital General de Castellón, Castellón, Spain
23HU Dr. J Trueta - Institut Català d'Oncologia, Girona, Spain
24HU Virgen de la Victoria, Málaga, Spain
25Hospital Universitario de Canarias, Universidad de La Laguna, Sta.Cruz Tenerife, Spain
26Hospital Universitario MarquéS De Valdecilla, Santander, ESP
27Hospital Parc Tauli, Sabadell, Barcelona, Spain
28Hematology department, Hospital Virgen de la Luz, Cuenca, Spain
29Hematology Department, Hospital Universitario de Burgos, Burgos, Spain
30Fundación Hospital Alcorcón, Alcorc N, Madrid, ESP
31Department of Hematology, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
32Hospital Universitario Puerto Real, Puerto Real, ESP
33University Hospital of La Princesa, Madrid, Spain
34Hospital Dr Peset, Valencia, Spain
35H Virgen de la Salud, Toledo, Spain
36Hospital Universitario Fundación Jiménez díaz, Madrid, Spain
37Complejo Hospitalario de Jaén, Jaen, ESP
38Hospital General de Castellón, Castellón De La Plana, Castellón, Spain
39Hospital de Jerez de la Frontera, Jerez De La Frontera, ESP
40Hospital Universitario Carlos Haya, Malaga, Spain
41Hematology Department, Hospital de Jerez de la Frontera, Jerez, Spain
42Hospital General Universitario Gregorio Marañon, Madrid, Spain
43Hospital Universitario de Salamanca, Salamanca, ESP
44Hospital Universitari MútuaTerrassa, Madrid, Spain
45Hospital General Universitario de Alicante, Madrid, Spain
46Hematology Department, University Hospital La Paz, Madrid, Spain., Hospital Universitario La Paz, Madrid, Spain
47Hematology Service, Hospital Universitario Ramón y Cajal. IRYCIS, Madrid, Spain

Introduction: Although Tyrosine Kinase Inhibitors (TKIs) have changed the natural history of chronic myeloid leukemia (CML), still a significant percentage of patients fail the TKIs available to date. Asciminib is a first-in-class BCR:ABL1 inhibitor specifically targeting the myristoyl pocket of ABL. Since adverse events (AEs) are mostly related to inhibition of non-target kinases by ATP-binding TKIs, asciminib could provide improved tolerability. Asciminib has demonstrated a good safety profile in clinical trials and in some preliminary studies in real clinical practice recently reported by several groups.

Our objective is to perform an analysis focused on the toxicities shown with asciminib, as well as to study the cross-intolerances with other TKIs, which may limit the expected success.

Materials and methods: We retrospectively studied 77 CML patients from 36 centers, who had presented a therapeutic failure to second-generation TKI. All of them received asciminib through a compassionate use program between Oct-2018 and June-2022. Statistical analysis was performed by SPSS using Fisher's exact test.

Results: the mean age at data collection was 66 years. 88% of patients had received ³3 TKIs previously. 34% had previously received ponatinib. Except for one patient who started in accelerated phase, the rest had chronic phase disease. Switching to asciminib was due to intolerance in 64% of patients. 25% had BCR-ABL mutations (4 patients T315I). Asciminib was initiated at a dose of 40mg BID, with the exception of patients with T315I mutation, who were initiated at 200mg BID.

Frequency of AEs is shown in Figure 1. 55% of patients had some AE with asciminib, most of them mild (grades 1-2), with 18% being grade 3-4. Most frequent AE were fatigue (18%), thrombocytopenia (17%), anemia (12%) and arthralgias (12%). None of the patients with previous cardiovascular events presented a new event. There were no cases of de novo occlusive peripheral arterial disease (PAD), although one patient experienced worsening of preexisting PAD.

In 20 patients a dose adjustment was required and in 19 of them a temporary suspension of treatment. The need for dose adjustment was more frequent in the intolerant group than in the group resistant to previous lines (33% vs 14%). Patients who required a dose reduction had an MMR rate at the end of follow-up of 55% (11/20) vs. 63% (34/54) in those who maintained standard doses. 8% (6/77) of patients had to stop treatment definitively due to side effects (pleural effusion, pneumonitis, renal failure, worsening of PAD, two due to pancreatitis).

When comparing AEs of asciminib versus previous classical TKIs, a lower percentage of cytopenias was observed (Fig.1b). For non-hematologic toxicities (Fig.1c), the frequency of AEs was visibly lower for the percentage of headache, pleural/pericardial effusion, diarrhea, and edema. No significant differences were observed for the rate of arthralgias, fatigue, abdominal pain and nausea.

Cross-intolerance with previous TKIs was analyzed for the most frequent AEs observed with asciminib (Table 1). Cross-toxicity risk was statistically significant for thrombopenia, anemia, neutropenia, fatigue, vomiting and pancreatitis. Cross-toxicity does not appear to affect the occurrence of cardiovascular events, edema, abdominal pain, diarrhea or rash. Cross intolerance led to treatment discontinuation in 5 patients (pleural effusion, pneumonitis, worsening of PAD, two cases of pancreatitis).

In terms of efficacy, 73% of patients maintained or achieved a complete cytogenetic response (CCyR) and 60% a major molecular response (MMR). Of the patients who had no prior response, 50% achieved CCyR and 49% achieved MMR. Responses were much better in patients who started asciminib for intolerance versus those who started it for resistance (80% of intolerant patients maintained or achieved MMR vs 26% in the resistant group).

With a median follow-up of 13,74 months a 71% of the patients continued treatment with asciminib. Of the total dropouts 7/22 (9% of total) were due to intolerance, 10/22 due to resistance and 5/22 due to death from any cause.

Conclusion: Asciminib is a molecule with a good safety profile, with a lower rate of AEs compared to classical TKIs. However, this drug, despite its novel mechanism of action presents risk of cross-intolerance with classical TKIs for some toxicities, including hematologic toxicity, fatigue, vomiting and pancreatitis.

Disclosures: Pérez-Lamas: Novartis: Research Funding. Giraldo: Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Acindes: Consultancy, Honoraria; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ZeroLMC Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lakhwani: Novartis: Honoraria; Janssen: Honoraria, Other: Advisory board. García Gutiérrez: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Research Funding.

<< Previous Abstract | Next Abstract
*signifies non-member of ASH