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Diagnosis and Upfront Therapy for CML

Insights From: Kendra Sweet, MD, Moffitt Cancer Center; Naval Daver, MD, University of Texas MD Anderson Cancer Center
Published: Thursday, Jan 12, 2017


Transcript:

Kendra Sweet, MD:
When managing a patient with chronic myeloid leukemia, the appropriate timing for running a kinase domain mutation analysis would be the time that a patient either misses a treatment milestone—so if their molecular testing results at a certain time point are not what we would expect or what we would hope—or in a patient who has previously met those milestones but then loses their response. That would be another time that you want to look at a mutation analysis. Doing it at the time a patient is diagnosed is not the time that we want to be looking because the chances of finding a mutation at that point are extremely low. So, we would just wait until a patient is not responding to treatment in the way that we would expect.

Naval Daver, MD: The standard monitoring of chronic myeloid leukemia has been done using PCR (polymerase chain reaction) technology. And our goal with most treatments has been to get patients into a major molecular response or, if possible, into a complete molecular response. The currently available PCR technologies are usually able to go down to levels of 10–4, or so, and are quite sensitive and have shown that in patients where we can get a major molecular response or a complete molecular response, this does correspond well with an event-free survival in those patients.

The digital process may be able to increase this by one log further. At this time, the clinical importance of such a deep remission is unknown, but I think as we’re getting prolonged follow-up on these patients, what we are starting to see is that it is really the patients who have a complete molecular remission that benefit. And so, it is quite possible that using the digital method of PCR, we may be able to get a more in-depth look at complete molecular remission that could result in a treatment-free survival. But, these studies will take many years, and long follow-up is yet to be determined.

Kendra Sweet, MD: When I see a newly, newly diagnosed CML patient and I’m trying to determine the most appropriate therapy for that person, I take into account a number of different factors, one being: the patient’s other medical conditions or comorbidities, the patient’s age, and the patient’s Sokal risk score. We have good data that show that patients with intermediate- and high-risk Sokal scores respond better and have better long-term outcomes when treated with second-generation TKIs (tyrosine kinase inhibitors). So, in that setting, I would try to use a second -generation TKI as frontline therapy rather than using imatinib. If we have somebody with a low-risk Sokal score, and maybe depending again on comorbidities, imatinib may be a better choice. So, all of those factors have to come into play when trying to determine the most appropriate therapy to use up front.

Naval Daver, MD: Upfront therapy in AML has, is a very interesting area. There are a number of options now available, which is good for physicians and the patients. At MD Anderson, our approach has been to use a second generation tyrosine kinase inhibitor up front. The data do show that the rates of major molecular remission, as well as complete molecular remission, at 12 months and 18 months are better using a second generation tyrosine kinase inhibitor.

Transcript Edited for Clarity
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Transcript:

Kendra Sweet, MD:
When managing a patient with chronic myeloid leukemia, the appropriate timing for running a kinase domain mutation analysis would be the time that a patient either misses a treatment milestone—so if their molecular testing results at a certain time point are not what we would expect or what we would hope—or in a patient who has previously met those milestones but then loses their response. That would be another time that you want to look at a mutation analysis. Doing it at the time a patient is diagnosed is not the time that we want to be looking because the chances of finding a mutation at that point are extremely low. So, we would just wait until a patient is not responding to treatment in the way that we would expect.

Naval Daver, MD: The standard monitoring of chronic myeloid leukemia has been done using PCR (polymerase chain reaction) technology. And our goal with most treatments has been to get patients into a major molecular response or, if possible, into a complete molecular response. The currently available PCR technologies are usually able to go down to levels of 10–4, or so, and are quite sensitive and have shown that in patients where we can get a major molecular response or a complete molecular response, this does correspond well with an event-free survival in those patients.

The digital process may be able to increase this by one log further. At this time, the clinical importance of such a deep remission is unknown, but I think as we’re getting prolonged follow-up on these patients, what we are starting to see is that it is really the patients who have a complete molecular remission that benefit. And so, it is quite possible that using the digital method of PCR, we may be able to get a more in-depth look at complete molecular remission that could result in a treatment-free survival. But, these studies will take many years, and long follow-up is yet to be determined.

Kendra Sweet, MD: When I see a newly, newly diagnosed CML patient and I’m trying to determine the most appropriate therapy for that person, I take into account a number of different factors, one being: the patient’s other medical conditions or comorbidities, the patient’s age, and the patient’s Sokal risk score. We have good data that show that patients with intermediate- and high-risk Sokal scores respond better and have better long-term outcomes when treated with second-generation TKIs (tyrosine kinase inhibitors). So, in that setting, I would try to use a second -generation TKI as frontline therapy rather than using imatinib. If we have somebody with a low-risk Sokal score, and maybe depending again on comorbidities, imatinib may be a better choice. So, all of those factors have to come into play when trying to determine the most appropriate therapy to use up front.

Naval Daver, MD: Upfront therapy in AML has, is a very interesting area. There are a number of options now available, which is good for physicians and the patients. At MD Anderson, our approach has been to use a second generation tyrosine kinase inhibitor up front. The data do show that the rates of major molecular remission, as well as complete molecular remission, at 12 months and 18 months are better using a second generation tyrosine kinase inhibitor.

Transcript Edited for Clarity
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