Oncology On The Go

S1 Ep183: Charting the Evolution of TKIs and Finding the Next Breakthrough in CML


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In a conversation with CancerNetwork®, Jorge Cortes, MD, explored the evolution of the chronic myeloid leukemia (CML) landscape. Specifically, he highlighted how the development of ibrutinib (Gleevec) paved the way for other tyrosine kinase inhibitors (TKIs) and described where research must go next in terms of implementing fixed-duration therapy and targeting genetic abnormalities.

Cortes, the director, and Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer at the Georgia Cancer Center, began by detailing the standards of care that existed before the development of imatinib. He noted that many patients did “not have great options,” as neither interferon nor transplant was associated with “good” outcomes. 

Following its approval for patients with CML in 2001, imatinib became what Cortes described as a “groundbreaker” in the field. He explained how imatinib’s newfound status as a standard of care in CML would signal the advancement of a second generation of TKIs, which included agents like dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif). Even with the subsequent development of third-generation TKIs, Cortes stated that researchers are continuing to improve and innovate to help provide patients with enhanced quality of life.

Looking towards the future, Cortes observed 2 major goals to achieve in CML research. The first objective is to stop therapy more effectively and give a greater portion of patients a more precisely defined duration of treatment. He noted that approximately 25% to 30% of patients today can effectively discontinue therapy without having to resume treatment, which wasn’t even considered a possibility in the field 20 years ago. Moreover, he emphasized that finding the therapeutic options that work best in a subset of patients with recently discovered genetic abnormalities may yield a breakthrough.

“In terms of whether we are getting closer to a cure, I think we are. We can stop therapy effectively in some patients, which is equivalent to a cure,” Cortes said. “If [a patient has] done well, and you can stop therapy and the disease doesn't come back, that's essentially what we think about as a cure. We are there, just not on as many patients as we want.”

Reference

Center for Drug Evaluation and Research: Application Number: NDA 21-335. FDA. May 10, 2001. Accessed October 6, 2025. https://tinyurl.com/44xh2u9j

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