Asciminib-a magic bullet for chronic myeloid leukemia with T315I mutation: a case series
DOI:
https://doi.org/10.18203/2320-6012.ijrms20233720Keywords:
CML, Asciminib, TKIsAbstract
Chronic myeloid leukemia (CML) is a type of myeloproliferative neoplasm typically characterized by the presence of the Philadelphia chromosome. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of most CML patients. However, resistance to TKIs poses a significant challenge, leading to poor treatment outcomes and prognosis in some patients. Fortunately, the introduction of asciminib, a novel allosteric BCR-ABL1 inhibitor, has provided a ray of hope. We present three cases in this report that highlight the remarkable efficacy of asciminib seen in our patients. All of these patients initially responded positively to conventional TKIs but developed a T315I mutation in the BCR-ABL fusion protein during their chemotherapy, rendering conventional TKIs ineffective and resulting in loss of response. Asciminib led to the achievement of a major molecular response in all of our patients.
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References
Verfaillie CM. Biology of chronic myelogenous leukemia. Hematol Oncol Clin North Am. 1998;12(1):1-29.
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2(5):561-6.
Bhatia R, Holtz M, Niu N, Gray R, Snyder DS, Sawyers CL et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood. 2003;101(12):4701-7.
Graham SM, Jørgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002;99(1):319-25.
O'Dwyer ME, Mauro MJ, Blasdel C, Farnsworth M, Kurilik G, Hsieh YC et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood. 2004;103(2):451-5.
Kantarjian HM, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101(2):473-5.
Kantarjian H, Talpaz M, O'Brien S, Giles F, Rios MB, White K et al. Prediction of initial cytogenetic response for subsequent major and complete cytogenetic response to imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer. 2003;97(9):2225-8.
Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol. 2005;23(18):4100-9.
Usva Z, Mohammed Y, Rikhia C, El-Nasir MAL, Afsar AM. The ''Gatekeeper'' Mutation T315I in BCR/ABL Confers Additional Oncogenic Activities to Philadelphia Chromosome Positive Leukemia. Blood. 2019;134(1):5196.
Jiao Q, Bi L, Ren Y, Song S, Wang Q, Wang YS. Advances in studies of tyrosine kinase inhibitors and their acquired resistance. Mol Cancer. 2018;17(1):36.
Cortes J, Quintás-Cardama A, Kantarjian HM. Monitoring molecular response in chronic myeloid leukemia. Cancer. 2011;117(6):1113-22.
Sacha T. Imatinib in chronic myeloid leukemia: an overview. Mediterr J Hematol Infect Dis. 2014;6(1):e2014007.
Cortes, J., Lang, F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14:44.
Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Abeloff's Clinical Oncology. 6th ed. Philadelphia, PA: Elsevier. 2020.
Vener C, Banzi R, Ambrogi F, Ferrero A, Saglio G, Pravettoni G et al. First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis. Blood Adv. 2020;4(12):2723-35.
Eide CA, Zabriskie MS, Savage Stevens SL, Antelope O, Vellore NA, Than H et al. Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants. Cancer Cell. 2019;36(4):431-3.
Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019;381(24):2315-26.
Sandeep P, Jorge C. Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery? Haematologica. 2023;108(11):2913-8.