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Early Molecular Responses in CML

Insights From: Kendra Sweet, MD, Moffitt Cancer Center; Naval Daver, MD, University of Texas MD Anderson Cancer Center; Javier Pinilla-Ibarz, MD, PhD, Moffitt Cancer Center
Published Online: Thursday, Mar 16, 2017



Transcript:

Javier Pinilla-Ibarz, MD, PhD:
In terms of choosing a first-generation versus second-generation TKI in order to achieve fast and deep molecular responses, I have to say that, in general, or at least in my practice, we use a second-generation TKI most of the time, with a goal to produce early molecular response that is very well associated with less event-free survival and overall survival. I have to say that it’s true that there have not been convincing data or evidence that dasatinib and nilotinib have superior overall survival in comparison with imatinib. However, we know that high- or intermediate-risk patients are the patients who maybe benefit the most from a second-generation TKI in order to decrease the rate of transformation in the first 1 to 2 years.

Also, I have to say that in the younger population, while you may argue that general population is everyone under 60 or even under 65, obtaining very early molecular response is very well associated with complete molecular response later on, once again opening the possibility to this great avenue of discontinuation that patients really, really wish for their future therapies. These days, this is part of the NCCN guidelines, and I think this is a great opportunity to introduce the second-generation TKI with the goals I already mentioned—early molecular response and fast response—so we can really, in the future, take them out of the drug.

Naval Daver, MD: At this time, the data do suggest that starting with the second-generation TKIs, mainly nilotinib or dasatinib, or potentially bosutinib, could result in a more rapid complete molecular, as well as major molecular remissions at 12 and 18 months. The question that a lot of community physicians have, or even academic physicians have, is will this translate into clinical outcome benefits for patients, such as improvement in overall survival or reductions in toxicities?

A number of these studies are being followed at this time, and it does seem that the curves are showing that there is a trend to improvement in event-free survival in patients who get the second-generation tyrosine kinase inhibitors. The overall survival data, at this time, do not show a significant improvement, but that may just be because these studies have now been around for only 8 or 9 years and we have often seen that for such chronic diseases, it may take 15 to 18 years. So, the answer would be, in general in leukemia as well as solid tumor, achievement of deeper remissions, whether they have been in complete or major molecular remissions, has always been associated with better survival outcomes in general. And so, our suggestion would be to consider second-generation tyrosine kinase inhibitors because they meet this parameter of a deeper response.

Javier Pinilla-Ibarz, MD, PhD: In terms of which factors I really consider when I stratify my patient, definitely age is an important one. However, age is also involved in the classical Sokal or Hasford criteria; very classical criteria that we have been using for many, many years—Sokal since the 80s, Hasford later on. Sokal comes from the interferon and transplant era, and definitely Hasford comes from after the introduction of interferon. EUTOS (European Treatment and Outcome Study) score has also been mainly used in Europe; less use in the United States. In my personal practice, in my environment, I really rely mostly on the Sokal score because it is the one that has produced better results in my case.

Transcript Edited for Clarity
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Transcript:

Javier Pinilla-Ibarz, MD, PhD:
In terms of choosing a first-generation versus second-generation TKI in order to achieve fast and deep molecular responses, I have to say that, in general, or at least in my practice, we use a second-generation TKI most of the time, with a goal to produce early molecular response that is very well associated with less event-free survival and overall survival. I have to say that it’s true that there have not been convincing data or evidence that dasatinib and nilotinib have superior overall survival in comparison with imatinib. However, we know that high- or intermediate-risk patients are the patients who maybe benefit the most from a second-generation TKI in order to decrease the rate of transformation in the first 1 to 2 years.

Also, I have to say that in the younger population, while you may argue that general population is everyone under 60 or even under 65, obtaining very early molecular response is very well associated with complete molecular response later on, once again opening the possibility to this great avenue of discontinuation that patients really, really wish for their future therapies. These days, this is part of the NCCN guidelines, and I think this is a great opportunity to introduce the second-generation TKI with the goals I already mentioned—early molecular response and fast response—so we can really, in the future, take them out of the drug.

Naval Daver, MD: At this time, the data do suggest that starting with the second-generation TKIs, mainly nilotinib or dasatinib, or potentially bosutinib, could result in a more rapid complete molecular, as well as major molecular remissions at 12 and 18 months. The question that a lot of community physicians have, or even academic physicians have, is will this translate into clinical outcome benefits for patients, such as improvement in overall survival or reductions in toxicities?

A number of these studies are being followed at this time, and it does seem that the curves are showing that there is a trend to improvement in event-free survival in patients who get the second-generation tyrosine kinase inhibitors. The overall survival data, at this time, do not show a significant improvement, but that may just be because these studies have now been around for only 8 or 9 years and we have often seen that for such chronic diseases, it may take 15 to 18 years. So, the answer would be, in general in leukemia as well as solid tumor, achievement of deeper remissions, whether they have been in complete or major molecular remissions, has always been associated with better survival outcomes in general. And so, our suggestion would be to consider second-generation tyrosine kinase inhibitors because they meet this parameter of a deeper response.

Javier Pinilla-Ibarz, MD, PhD: In terms of which factors I really consider when I stratify my patient, definitely age is an important one. However, age is also involved in the classical Sokal or Hasford criteria; very classical criteria that we have been using for many, many years—Sokal since the 80s, Hasford later on. Sokal comes from the interferon and transplant era, and definitely Hasford comes from after the introduction of interferon. EUTOS (European Treatment and Outcome Study) score has also been mainly used in Europe; less use in the United States. In my personal practice, in my environment, I really rely mostly on the Sokal score because it is the one that has produced better results in my case.

Transcript Edited for Clarity
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