P708: Canadian and Russian Experiences of Asciminib in Chronic Myeloid Leukemia (Cml) Patients Who Failed Multiple Lines of Tyrosine Kinase Inhibitor (Tki) Therapy.

Khadadah, Fatima; Turkina, Anna; Lomaia, Elza; Morozova, E. V.; Shukhov, Oleg; Petrová, Anna; Chitanava, Tamara; Vlasova, J. J.; Kuzmina, Elena; Nemchenko, Irina; Chelysheva, Ekaterina; Bykova, Anastasiya; Gurianova, Margarita; Xenocostas, Anargyros; Busque, Lambert; Jamani, Kareem; Cerquozzi, S.; Kuruvilla, Philip; Kaedbey, R.; Leber, Brian; Assouline, Sarit; Kim, D. D. H.

doi:10.1097/01.hs9.0000845716.75856.2d

Cited by 6 publications

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“…In over 200 patients treated, the CCyR rates ranged from 57% to 70%, the MMR rates ranged from 22% to 53%, and the DMR/MR4 rates ranged from 16% to 42%. [120][121][122][123] Currently, there are no randomized head-to-head trials comparing ponatinib and asciminib in CML. As third-line therapy, among 82 patients treated with asciminib 40 mg BID, the MMR rate was 30.5% and the CCyR rate was 40.8%.…”

Section: Second and Third Generation Tkismentioning

confidence: 99%

“…At the EHA 2022 annual meeting, the results of asciminib (free‐drug supply) in patients with CML post 3+ TKIs from different countries were reported (Russia, Canada, Italy, United Kingdom, Netherland). In over 200 patients treated, the CCyR rates ranged from 57% to 70%, the MMR rates ranged from 22% to 53%, and the DMR/MR4 rates ranged from 16% to 42% 120–123 …”

Section: Management Of Tki Resistancementioning

confidence: 99%

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Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

2022

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Disease Overview Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. Diagnosis CML is characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Frontline Therapy Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib are approved by the United States Food and Drug Administration for first‐line treatment of newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. Salvage Therapy For CML post failure on frontline therapy, second‐line options include second and third generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs, and for all patients in advanced phase disease. Older patients who have a cytogenetic relapse post failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan and others).

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Section: Second and Third Generation Tkismentioning

confidence: 99%

Section: Management Of Tki Resistancementioning

confidence: 99%

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

2022

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“…Прием асциминиба прекратило 15 пациентов, в т. ч. из-за неэффективности лечения (n = 11), прогрессирования заболевания до БК (n = 3), тромбоцитопении IV степени (n = 1). Сердечно-сосудистых НЯ не отмечалось [41].…”

Section: лечение резистентного хмлunclassified

Результаты Применения Асциминиба, Первого Аллостерического Ингибитора BCR::ABL1-тирозинкиназы, У Больных Хроническим Миелолейкозом Со Множественной Резистентностью К Предшествующей Терапии

Туркина,

Кузьмина

2024

Clinical Oncohematology

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Currently, there is a crucial need for new treatment approaches to overcome the resistance and intolerance of several tyrosine kinase inhibitor (TKI) therapy lines in chronic myeloid leukemia (CML) patients. Asciminib, the first in its class BCR::ABL1-tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket (STAMP), demonstrated efficacy and safety in CML patients with prior TKI therapy failure, including the cases with pan-resistant T315I mutation in the chimeric BCR::ABL1 gene. The present review focuses on the asciminib mechanism of action, the results of both preclinical and clinical phase I and III studies. Due to the favorable cardiovascular toxicity profile of asciminib, the scope of its application can be extended to patients with cardiovascular co-morbidities. Asciminib is registered in the Russian Federation in January 2023, so treatment algorithms for CML patients with ineffectiveness or intolerance of prior therapy should be updated in line with this new option.

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Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring

Jabbour,

Kantarjian

2024

American J Hematol

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Disease overviewChronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.DiagnosisCML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein.Frontline therapyFour tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first‐line treatment of newly diagnosed CML in the chronic phase (CML‐CP). Clinical trials with second and third‐generation TKIs in frontline CML‐CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high‐risk disease and in whom the aim of therapy is to induce a treatment‐free remission status, second‐generation TKIs may be favored.Salvage therapyFor CML post‐failure on frontline therapy, second‐line options include second and third‐generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs and for all patients in advanced‐phase disease. Older patients who have a cytogenetic relapse post‐failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).

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P708: Canadian and Russian Experiences of Asciminib in Chronic Myeloid Leukemia (Cml) Patients Who Failed Multiple Lines of Tyrosine Kinase Inhibitor (Tki) Therapy.

Cited by 6 publications

References 0 publications

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring

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