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FAQ: What are the Warning Signs of Resistance?

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Jorge Cortes, MD explains how to identify the clinical signs of resistance in patients in later lines of chronic myeloid leukemia (CML)

Content intended for health care professionals.

Target CML

Unmet Needs in CML

Expert Perspectives in CML

By later lines of CML, patients may experience increased intolerance and resistance1-6

Links: Intolerance Resistance Overall survival Patient profiles
Resistance Overall survival Patient profiles
Intolerance
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Intolerance

After multiple lines of ATP-competitive TKIs, patients may face intolerance challenges7-11

In patients with CML in ≥2 TKIs up to 55% were intolerant to a previous TKI In patients with CML in ≥2 TKIs up to 55% were intolerant to a previous TKI

Even low-grade, chronic TKI intolerance can impact compliance with therapy, which in turn can lead to poor outcomes14,15

TKI intolerance may negatively influence compliance of CML therapies

  • In a survey of patients with CML, nearly half of responders skipped doses of their medication—many to reduce adverse events16
  • In turn, lower compliance with therapy for CML may impact outcomes for patients14,17,18
Impact of noncompliance on achievement of MMR. Impact of noncompliance on Event Free Survival (2-year EFS) Impact of noncompliance on achievement of MMR. Impact of noncompliance on Event Free Survival (2-year EFS)

Patients with lower compliance rates had:

  • Significantly higher risk of suboptimal response (P=0.005)19
  • Significantly lower rates of CCyR (P=0.004)19
cameraWatch video of Dr Talpaz on how he approaches patients facing intolerance

Resistance

Patients who experienced resistance after 2 or more TKIs may need a different treatment strategy

In a Phase ½ study of 118 patients receiving bosutinib who had been previously treated with ≥2 TKIs: Only 24% of patients achieved CCyR. Only 15% of patients achieved MMR. In a Phase ½ study of 118 patients receiving bosutinib who had been previously treated with ≥2 TKIs: Only 24% of patients achieved CCyR. Only 15% of patients achieved MMR.
cameraSee video of how Dr Cortes approaches patients who are resistant to treatment

Overall survival

Using line after line of ATP-competitive TKIs may lead to increased failure rates2,21,22

  • New mutations from ATP-competitive TKI use can result in limited sensitivity to some TKIs1
  • Potential resistance or intolerance in second- and third-line may result in poorer efficacy outcomes and increased risk of discontinuation2,3
8-year overall survival is 83% in first line and 22% OS in third line (based on a retrospective, single-center analysis) 8-year overall survival is 83% in first line and 22% OS in third line (based on a retrospective, single-center analysis)
cameraSee video on when Dr Cortes knows it’s time to change treatment strategy

Patient profiles

Assessing different patient scenarios in later lines of CML

Consider a patient experiencing potential drug resistance
Download Patient Profile download icon
View a profile of a patient experiencing a borderline response
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Review a patient having difficulty tolerating treatment
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Not actual patients.

Did you know?

Up to 25% of patients with CML discontinue therapy due to adverse events23-26

Many patients treated with 2L TKIs are still at higher risk of experiencing TKI intolerance6,10,27

  • This can happen despite management of treatment-related AEs with dose reductions, transient treatment interruptions, supportive care, and concomitant medications6,10,27

Health care providers may have different perceptions of tolerability compared to patients and this disconnect can negatively impact patient care23,28

Wondering how experts approach CML in later lines?

Watch now

ATP, adenosine 5’-triphosphate; CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; MMR, major molecular response; 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. Ongoren S, Eskazan AE, Suzan V, et al. Hematology. 2017;23(4):212-220. 13. Giles FJ, Abruzzese E, Rosti G, et al. Leukemia. 2010;24(7):1299-1301. 14. Marin D, Bazeos A, Mahon F-X, et al. J Clin Oncol. 2010;28(14):2381-2388. 15. Kim D-W, Saussele S, Williams LA, et al. Ann Hematol. 2018;97(8):1357-1367. 16. Eliasson L, Clifford S, Barber N, Marin D. Leuk Res. 2011;35(5):626-630. 17. Ibrahim AR, Eliasson L, Apperley JF, et al. Blood. 2011;117(14):3733-3736. 18. Hochhaus A, Baccarani M, Silver RT, et al. Leukemia. 2020;34(4):966-984. 19. Noens L, van Lierde M-A, De Brock R, et al. Blood. 2009;113(22):5401-5411. 20. Khoury HJ, Cortes JE, Kantarjian HM, et al. Blood. 2012;119(15):3403-3411. 21. Bosi GR, Fogliatto LM, Costa TEV, et al. Hematol Transfus Cell Ther. 2019;41(3):222-228. 22. Iacob RE, Zhang J, Gray NS, Engen JR. PLoS One. 2011;6(1):e15929. 23. Cortes JE, Kim D-W, Pinilla-Ibarz J, et al. Blood. 2018;132(4):393-404. 24. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. J Clin Oncol. 2018;36(3):231-237. 25. Hochhaus A, Saglio G, Hughes T, et al. Leukemia. 2016;30(5):1044-1054. 26. Hochhaus A, Gambacorti-Passerini C, Abboud C, et al. Leukemia. 2020;34(8):2125-2137. 27. Kantarjian HM, Cortes JE, Kim D-W, et al. Blood. 2014;123(9):1309-1318. 28. Efficace F, Rosti G, Aaronson N, et al. Haematologica. 2014;99(4):788-793.

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