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The NILSt and D-STOP Trials 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: Wednesday, Mar 29, 2017


Transcript:

Javier Pinilla-Ibarz, MD, PhD:
The NILSt trial tried to address the success rate of discontinuation of nilotinib after at least 2 years of complete molecular response, or what we call pCR, of more than 4.5 log reduction. In this trial, the success rate of discontinuation is close to 60%; in this case, 58.9%. And this once again has reproduced the same data that other trials have been demonstrating in the last 5 years.

The NILSt trial, once again putting in the study of treatment discontinuation, has reproduced what we have already previously seen in many other trials. Discontinuation after at least 2 years of MR 4.5, or what we call complete molecular response, is something that may be feasible. In terms of how many patients really successfully discontinue, I think we see the same percentage after a first- or second-generation TKI. And we are talking about numbers between 40% and 60%, depending on the population that we study. It is very interesting that we thought of second-generation TKIs maybe having higher rates of success, but what is really important to really point out is that although we see the same percentage of treatment failure discontinuation success, the pool of patients that can be discontinued is larger, or at least is doubled ,when we compare a frontline or first-generation TKI with a second-generation TKI.

The D-STOP trial is another Japanese trial that tried to address the discontinuation or the success of discontinuation in patients treated with dasatinib. The interesting aspect of this trial is it also tried to address if any specific population of lymphocyte that has been associated with some of the effects of dasatinib has any relation with the success of discontinuations. Once again—and as we have seen in multiple previous trials with imatinib or with nilotinib—very interestingly, we see a success rate of around 60% of the year. It’s true, also, that most of the failures or the molecular relapses that have been seen in this and other trials happen in the first 6 months. In fact, almost 80% of the patients will relapse shortly after. But there is a small percentage of patients that may have late relapses. Once again, the results of this trial confirm the possibility to discontinue patients, in this case with dasatinib, but very, very similar to the data that have been obtained on nilotinib as well as with imatinib.

The monitoring of patients after treatment cessation is quite important. In fact, it’s fundamental to guarantee the safety of our patients while we try these interventions. The guidelines, like the NCCN guidelines and the other trial that has been performed in France and other parts of the world always recommend to have a monthly pCR for the first 6 months to intervene early. In this case, the reason of intervention will be the loss of MMR or, in this case, pCR of more than 0.1%. That will be the threshold in which we need to start therapy with TKI, most of the time with the same TKI. And most of those patients will recover the same response that they had before. After 6 months of monthly follow-up, we try to extend this period of time to every 2 months. This is defined in between 6 and 12 months. And after this time, and the patient still successfully discontinues with the lack of relapse, we can go to the 3 months. And of course, later on, we can start to space them. However, it’s important to point out that those patients should be followed even for longer periods of times because there have been late relapses described. I think with a pCR test, we should, or we can, avoid these late, late relapses.

Transcript Edited for Clarity
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Transcript:

Javier Pinilla-Ibarz, MD, PhD:
The NILSt trial tried to address the success rate of discontinuation of nilotinib after at least 2 years of complete molecular response, or what we call pCR, of more than 4.5 log reduction. In this trial, the success rate of discontinuation is close to 60%; in this case, 58.9%. And this once again has reproduced the same data that other trials have been demonstrating in the last 5 years.

The NILSt trial, once again putting in the study of treatment discontinuation, has reproduced what we have already previously seen in many other trials. Discontinuation after at least 2 years of MR 4.5, or what we call complete molecular response, is something that may be feasible. In terms of how many patients really successfully discontinue, I think we see the same percentage after a first- or second-generation TKI. And we are talking about numbers between 40% and 60%, depending on the population that we study. It is very interesting that we thought of second-generation TKIs maybe having higher rates of success, but what is really important to really point out is that although we see the same percentage of treatment failure discontinuation success, the pool of patients that can be discontinued is larger, or at least is doubled ,when we compare a frontline or first-generation TKI with a second-generation TKI.

The D-STOP trial is another Japanese trial that tried to address the discontinuation or the success of discontinuation in patients treated with dasatinib. The interesting aspect of this trial is it also tried to address if any specific population of lymphocyte that has been associated with some of the effects of dasatinib has any relation with the success of discontinuations. Once again—and as we have seen in multiple previous trials with imatinib or with nilotinib—very interestingly, we see a success rate of around 60% of the year. It’s true, also, that most of the failures or the molecular relapses that have been seen in this and other trials happen in the first 6 months. In fact, almost 80% of the patients will relapse shortly after. But there is a small percentage of patients that may have late relapses. Once again, the results of this trial confirm the possibility to discontinue patients, in this case with dasatinib, but very, very similar to the data that have been obtained on nilotinib as well as with imatinib.

The monitoring of patients after treatment cessation is quite important. In fact, it’s fundamental to guarantee the safety of our patients while we try these interventions. The guidelines, like the NCCN guidelines and the other trial that has been performed in France and other parts of the world always recommend to have a monthly pCR for the first 6 months to intervene early. In this case, the reason of intervention will be the loss of MMR or, in this case, pCR of more than 0.1%. That will be the threshold in which we need to start therapy with TKI, most of the time with the same TKI. And most of those patients will recover the same response that they had before. After 6 months of monthly follow-up, we try to extend this period of time to every 2 months. This is defined in between 6 and 12 months. And after this time, and the patient still successfully discontinues with the lack of relapse, we can go to the 3 months. And of course, later on, we can start to space them. However, it’s important to point out that those patients should be followed even for longer periods of times because there have been late relapses described. I think with a pCR test, we should, or we can, avoid these late, late relapses.

Transcript Edited for Clarity
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