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Target CML

Unmet Needs in CML

Expert Perspectives in CML

Later lines of CML may be associated with increased intolerance and resistance.1,6

After multiple lines of ATP-competitive TKIs, patients may face intolerance challenges.7-11 Even low-grade, chronic TKI intolerance can impact compliance with therapy, which in turn can lead to poor outcomes.12,13

Resistance challenges also can become more common with later lines of ATP-competitive TKIs and using line after line of these therapies may lead to increased failure rates.2,14,15

What experts from around the world say...

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“…when a patient has already resistance to a second-generation tyrosine kinase inhibitor, what do you do next? …it is a complicated scenario, and it is one that emphasizes the need for additional treatment options.”

Jorge Cortes, MD. Georgia Cancer Center, USA

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“…the tolerability issues of current TKIs for many patients highlight the need for new therapies.”

Eri Matsuki, MD. Keio University Hospital, Tokyo, Japan

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“Resistance will continue to compromise our ability to promote long-term survival for our patients with CML, highlighting the need for a new therapy.”

Carla Boquimpani, MD. Hospital Hemorio, Rio de Janeiro, Brazil

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“…from a clinical perspective, this approach of cycling through these [ATP-competitive] TKIs is not ideal, since resistance mutations in the ATP-binding site may render other TKIs ineffective, manifesting as multidrug resistance and impeding the potential to overcome resistance.”

Jorge Cortes, MD. Georgia Cancer Center, USA

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“We, as oncologists, tend to rely on the big-time toxicities, and say, well, minor toxicities, please tolerate it. But, please understand, this is chronic treatment given over a long period of time, and quality of life of the patient is critical.”

Moshe Talpaz, MD. University of Michigan, USA

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“Dose adjustment, particularly a dose increase of a tyrosine kinase inhibitor, has sometimes been used for patients who are developing suboptimal response or a resistance to therapy. However, in some studies, there has been compared that strategy versus changing, and changing tends to be better.”

Jorge Cortes, MD. Georgia Cancer Center, USA

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ATP, adenosine 5’-triphosphate; CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor.

References: 1. Soverini S, Gnani A, Colarossi S, et al. Blood. 2009;114(10):2168-2171. 2. Garg RJ, Kantarjian H, O'Brien S, et al. Blood. 2009;114(20):4361-4368. 3. Ibrahim AR, Paliompeis C, Bua M, et al. Blood. 2010;116(25):5497-5500. 4. Gambacorti-Passerini C, Brummendorf TH, Kim D-W, et al. Am J Hematol. 2014;89(7):732-742. 5. Shah NP, Kim D-W, Kantarjian H, et al. Haematologica. 2010;95(2):232-240. 6. Kantarjian HM, Giles FJ, Bhalla KN, et al. Blood. 2011;117(4):1141-1145. 7. Cortes JE, Khoury HJ, Kantarjian HM, et al. Am J Hematol. 2016;91(12):1206-1214. 8. Cortes JE, Kim D-W, Pinilla-Ibarz J, et al. N Engl J Med. 2013;369(19):1783-1796. 9. Kim TD, Schwarz M, Nogai H, et al. Thyroid. 2010;20(11):1209-1214. 10. Quintás-Cardama A, Kantarjian H, O'Brien S, et al. J Clin Oncol. 2007;25(25):3908-3914. 11. Cortes J, Mauro M, Steegmann JL, et al. Am J Hematol. 2015;90(4):E66-E72. 12. Marin D, Bazeos A, Mahon F-X, et al. J Clin Oncol. 2010;28(14):2381-2388. 13. Kim D-W, Saussele S, Williams LA, et al. Ann Hematol. 2018;97(8):1357-1367. 14. Bosi GR, Fogliatto LM, Costa TEV, et al. Hematol Transfus Cell Ther. 2019;41(3):222-228. 15. Iacob RE, Zhang J, Gray NS, Engen JR. PLoS One. 2011;6(1):e15929.

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