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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)

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Consider an earlier switch for patients with intolerance and/or suboptimal response

Links: Intolerance Suboptimal response
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Intolerance
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Intolerance

“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

Patients with intolerance may need a treatment switch

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 outcomes3,4

Failure to address TKI intolerance may negatively influence compliance of CML therapies.

  • In a survey of patients with CML, nearly half of responders missed doses of their medication—mostly to reduce adverse events5
  • In turn, lower compliance with therapy for CML may impact outcomes for patients3,6,7
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)8
  • Significantly lower rates of CCyR (P=0.004)8
cameraWatch video of Dr Talpaz discussing if switching due to low grade AEs is appropriate.

Did you know?

Up to 25% of patients with CML discontinue therapy due to AEs.7,9-11

Many patients treated with 2L TKIs are still at higher risk of experiencing TKI intolerance.12-14

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

Health care providers may have different perceptions of tolerability compared with patients and this disconnect can negatively impact patient care.15

Suboptimal Response

Patients who experience suboptimal response may need a different treatment strategy

“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

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

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AE, adverse event; ATP, adenosine 5’-triphosphate; CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; EFS, event-free survival; MMR, major molecular response; TKI, tyrosine kinase inhibitor.

References: 1. Ongoren S, Eskazan AE, Suzan V, et al. Hematology. 2018;23(4):212-220. 2. Giles FJ, Abruzzese E, Rosti G, et al. Leukemia. 2010;24(7):1299-1301. 3. Marin D, Bazeos A, Mahon F-X, et al. J Clin Oncol. 2010;28(14):2381-2388. 4. Kim D-W, Saussele S, Williams LA, et al. Ann Hematol. 2018;97(8):1357-1367. 5. Eliasson L, Clifford S, Barber N, Marin D. Leuk Res. 2011;35(5):626-630. 6. Ibrahim AR, Eliasson L, Apperley JF, et al. Blood. 2011;117(14):3733-3736. 7. Hochhaus A, Baccarani M, Silver RT, et al. Leukemia. 2020;34(4):966-984. 8. Noens L, van Lierde M-A, De Brock R, et al. Blood. 2009;113(22):5401-5411. 9. Cortes JE, Kim D-W, Pinilla-Ibarz J, et al. Blood. 2018;132(4):393-404. 10. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. J Clin Oncol. 2018;36(3):231-237. 11. Hochhaus A, Saglio G, Hughes TP, et al. Leukemia. 2016;30(5):1044-1054. 12. Kantarjian HM, Giles FJ, Bhalla KN, et al. Blood. 2011;117(4):1141-1145. 13. Quintás-Cardama A, Kantarjian H, O'Brien S, et al. J Clin Oncol. 2007;25(25):3908-3914. 14. Kantarjian HM, Cortes JE, Kim D-W, et al. Blood. 2014;123(9):1309-1318. 15. Efficace F, Rosti G, Aaronson N, et al. Haematologica. 2014;99(4):788-793. 16. Khoury HJ, Cortes JE, Kantarjian HM, et al. Blood. 2012;119(15):3403-3411.

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