CML: Challenges and Unmet Needs in Later-Line Therapy

A brief review of the inherent challenges in guiding patients through several lines of therapy for chronic myeloid leukemia.


Jorge E. Cortes, MD: In the frontline studies, when we look at the long-term follow-up analyses, by 5 years approximately 40% of patients have required a change of therapy. That’s from the first-line therapy. By 10 years, it’s about 50% of patients who have required a change of therapy. With second-line therapy, we only get a complete cytogenetic response in about 40% of patients. So that means that at least 60% of those will also need change. I think in the end, anywhere between 25% and 40% of patients will require a change of therapy, even when we strictly adhere to the definitions of resistance or intolerance. Sometimes patients change therapy because of other indications, of optimal response or low-grade toxicity, and that adds to those percentages. But I do think that, at the very least, even if you’re very strict on your definitions, somewhere between 25% and 40% of patients will require a change of therapy, at some point.

I think it is important to remember that this is a chronic disease. And many times, patients are doing well, they look good, and they feel well, even when we recognize resistance. But we have to recognize that developing resistance, and therefore moving to a second, then a third, and then a fourth TKI [tyrosine kinase inhibitor], decreases the probability of survival. So it is not just a cosmetic issue, it is not just a number that you’re managing. When a patient truly develops resistance, it is important to get a good treatment option because although the patient may not feel bad, may not have any immediate obvious concerns, in the long term, it decreases the probability of survival. We had done an analysis some years ago, and we established that, when the patient moves to a second TKI, and then to a third TKI, and then a fourth TKI, the survival probability by 5 years drops to 80%, then to 60%, then to 40%. So it is really a meaningful event that needs attention and proper action.

Transcript edited for clarity.

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