Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Patel AB, O’Hare T, Deininger MW. Mechanisms of resistance to ABL kinase inhibition in chronic myeloid leukemia and the development of next generation ABL kinase inhibitors. Hematol Oncol Clin N Am. 2017;31:589–612.

Article  Google Scholar 

Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14:44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Akard LP, Albitar M, Hill CE, Pinilla-Ibarz J. The “hit hard and hit early” approach to the treatment of chronic myeloid leukemia: implications of the updated National Comprehensive Cancer Network clinical practice guidelines for routine practice. Clin Adv Hematol Oncol. 2013;11:421–32.

Google Scholar 

Jabbour E, Kantarjian H, Cortes J. Use of second- and third-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia: an evolving treatment paradigm. Clin Lymphoma Myeloma Leuk. 2015;15:323–34.

Article  PubMed  PubMed Central  Google Scholar 

Bosi GR, Fogliatto LM, Costa TEV, Grokoski KC, Pereira MP, Bugs N, et al. What happens to intolerant, relapsed or refractory chronic myeloid leukemia patients without access to clinical trials? Hematol Transfus Cell Ther. 2019;41:222–8.

Article  PubMed  PubMed Central  Google Scholar 

Jabbour E, Parikh SA, Kantarjian H, Cortes J. Chronic myeloid leukemia: mechanisms of resistance and treatment. Hematol Oncol Clin N Am. 2011;25:981–95.

Article  Google Scholar 

Nicolini FE, Ibrahim AR, Soverini S, Martinelli G, Muller MC, Hochhaus A, et al. The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis. Haematologica. 2013;98:1510–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Soverini S, Branford S, Nicolini FE, Talpaz M, Deininger MW, Martinelli G, et al. Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia. Leuk Res. 2014;38:10–20.

Article  CAS  PubMed  Google Scholar 

Dhillon S. Olverembatinib: first approval. Drugs. 2022;82:469–75.

Article  CAS  PubMed  Google Scholar 

Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876–80.

Article  CAS  PubMed  Google Scholar 

Manley PW, Barys L, Cowan-Jacob SW. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase. Leuk Res. 2020;98:106458.

Article  CAS  PubMed  Google Scholar 

Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393–404.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deininger MW, Apperley JF, Arthur CK, Chuah C, Hochhaus A, De Lavallade H, et al. Post hoc analysis of responses to ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) By baseline BCR-ABL1 level and baseline mutation status in the OPTIC Trial. Blood. 2021;138:307.

Article  Google Scholar 

Boddu P, Shah AR, Borthakur G, Verstovsek S, Garcia-Manero G, Daver N, et al. Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting. Leuk Lymphoma. 2018;59:1312–22.

Article  CAS  PubMed  Google Scholar 

Cortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021;138:2042–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Molica M, Scalzulli E, Colafigli G, Foa R, Breccia M. Insights into the optimal use of ponatinib in patients with chronic phase chronic myeloid leukaemia. Ther Adv Hematol. 2019;10:2040620719826444.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iclusig (Ponatinib) [package insert]. Cambridge MTPCL.

Jabbour E, Kantarjian H, O’Brien S, Shan J, Quintas-Cardama A, Faderl S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood. 2011;118:4541–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011;29:1634–42.

Article  CAS  PubMed  Google Scholar 

Jabbour E, Apperley J, Cortes J, Rea D, Deininger M, Abruzzese E, et al. Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the PACE and OPTIC trials. Leukemia. 2024;38:475–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schoepfer J, Jahnke W, Berellini G, Buonamici S, Cotesta S, Cowan-Jacob SW, et al. Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1. J Med Chem. 2018;61:8120–35.

Article  CAS  PubMed  Google Scholar 

Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, et al. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature. 2017;543:733–7.

Article  CAS  PubMed  Google Scholar 

Rea D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138:2031–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mauro MJ, Hughes TP, Kim D-W, Réa D, Cortes JE, Hochhaus A, et al. Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-Year phase 1 safety and efficacy results. Leukemia. 2023;37:1048–59.

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;381:2315–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Novartis Pharmaceuticals Corporation. NDA/BLA Multi-disciplinary Review and Evaluation SCEMBLIX (asciminib). 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/215358Orig1s000,Orig2s000MultidisciplineR.pdf. Accessed 29 Apr 2024.

Combes FP, Li YF, Hoch M, Lorenzo S, Ho YY, Sy SKB. Exposure-efficacy analysis of asciminib in Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Clin Pharmacol Ther. 2022;112:1040–50.

Scemblix (asciminib) [package insert]. East Hanover, NJ; Novartis Pharmaceutical Corporation. 2023.

Hughes TP, Cortes JE, Réa D, Mauro MJ, Hochhaus A, Kim D-W, et al. Asciminib provides durable molecular responses in patients with chronic myeloid leukemia in chronic phase (CML-CP) with the T315I mutation: updated efficacy and safety data from a phase I trial. Presented at: EHA2022 Congress; June 9-17, 2022; Vienna, Austria, and Online. Poster P704.

Scemblix (asciminib) [prescribing information]. Macquarie Park N, Australia; Novartis Pharmaceuticals Australia Pty Limited; 2022.

Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castagnetti F, Gugliotta G, Breccia M, Stagno F, Iurlo A, Albano F, et al. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib. Leukemia. 2015;29:1823–31.

Article  CAS  PubMed  Google Scholar 

Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.

Article  CAS  PubMed  Google Scholar 

Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369:1783–96.

Article  CAS  PubMed  Google Scholar 

Hehlmann R, Lauseker M, Saussele S, Pfirrmann M, Krause S, Kolb HJ, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31:2398–406.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boque C, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cortes J, Quintas-Cardama A, Kantarjian HM. Monitoring molecular response in chronic myeloid leukemia. Cancer. 2011;117:1113–22.

Article  CAS  PubMed  Google Scholar 

Hehlmann R, Muller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol. 2014;32:415–23.

Article  PubMed  Google Scholar 

Falchi L, Kantarjian HM, Wang X, Verma D, Quintas-Cardama A, O’Brien S, et al. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol. 2013;88:1024–9.

Article  CAS