Ongoing Studies in CML-CP Offer Hope to Future Treatments

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Talha Badar, MBBS, MD, discussed ongoing trials in the treatment of chronic myeloid leukemia in chronic phase, as well as his hope for future therapies in the space.

As part of CancerNetwork’s Face-Off video series, Talha Badar, MBBS, MD, assistant professor of oncology, Mayo Clinic, discussed current treatments being evaluated for chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs).

In addition, he offered his future outlook on the space, and what is to come in the treatment of this disease.

Badar: There's another phase 1 trial of imatinib, which is a third generation TKI. And that is ongoing in various centers in North America as well as Europe, in which they're trying to validate the safety and efficacy in patients who had CML in chronic phase who had 2 prior lines of TKI. So the interesting observation that study in patients who failed on ponatinib [Iclusig] tends to have a response with imatinib, a third generation TKI. So that's encouraging.

And well, this is all about the patients who are progressing with their second generation TKI and how to control the disease. There is another aspect of it is in treatment-naive patients whom you are planning to initiate therapy for CML, how you can improve the treatment-free duration or treatment-free response in those patients. Historically, we know if you achieve a major marker response and you maintain that response for 2 years, there is a possibility that you can come off of medication and maintain treatment-free duration in 50% of patients; however, 50% of patients would need to go back on therapy after losing molecular response.

In that setting. There are various studies ongoing in which evaluating the addition of asciminib (Scemblix) to imatinib, which are 2 different CML therapies who work mechanistically differently and try to achieve proportion of patients achieving treatment-free response and that is more relevant in patients who are younger in age and would like to have a treatment-free period and doesn't want to continue lifelong with these therapies. So, that is something the initial results are encouraging and more to follow in that space.

The other aspect is CML other chronic hematologic malignancies and chronic leukemias, they tend to evolve with time. And there are various mechanisms in which patients lose response and a certain subset of patient progress to more advanced stage disease, including blastic-phase CML. And what we learned through the retrospective analysis and these patients developed somatic mutations, and that made them resistant to therapy and that evolved the disease to more leukemia. So there is analysis from the TIGER study, a German study of the cigna in patients in a chronic phase in which they did see real monitoring of the myeloid mutation panel. And they figured out various somatic mutations patients acquired during the treatment course. And 1 of the mutations that predict inferior outcome was XL1 mutation, which we commonly seen in MDS and AML. So seated monitoring, through a method to look for resistant mutation, that may help in preemptively initiating or having strategies to how to overcome them, how to improve the outcome of our patients, something to look for in a for in future prospective studies.

I would like to give the best therapy upfront to have a best response and long-lasting response rather than sequencing these therapies to first-generation TKI, to second-generation TKI, and third-generation TKI and then look for novel concepts. If we can prove that using newer therapies, third-generation TKI or novel therapies with better tolerability, will make an impact in overall survival, improving outcomes in these patients, improving quality of life, that will be something really great in this space and something to look for.

Transcription edited for clarity.

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