Treatment-Free Remission in CML

Transcript:Kendra Sweet, MD: More data keep coming out showing us that TKI therapy can be safely discontinued in a select group of CML patients. It appears that in chronic-phase CML patients who have achieved deep levels of molecular response, in most cases that means at least MR 4.0 and they have maintained that response for a reasonably long duration of time—1 year, 2 years, or 3 years. In that setting, it’s reasonable to consider an attempt at TKI discontinuation. We want to make sure that when we’re doing this, we have patients who we know are reliable and will come back and continue to get their molecular testing done. They need to be treated by someone who has access to reliable pCR that’s reported on the international scale. We want to make sure that whoever is attempting to discontinue the TKI with the patient, whichever physician is doing it, is aware of all of the data and aware of when most studies have restarted TKI therapy. But in this day and age, discontinuation of TKIs is becoming a very real possibility for a select group of patients, which I think is very exciting.

Javier Pinilla-Ibarz, MD, PhD: Treatment-free remission is a very important topic in the treatment of chronic myeloid leukemia in 2017. The NCCN, for the first time, has laid out the basis of outside clinical trials where we can discontinue patients that have been treated on TKIs for a certain period of time. And, in general, although these rules may change—and we know that the longer the therapy, the better it is considered—if a patient has been taking a first- or second-generation TKI for more than 3 months and at least has been in a complete molecular response, or is at least achieving a 4.0 logs reduction over pCR, that is a patient that may be considered a candidate for discontinuation. However, I have to say that, of course, there are other parameters that need to be considered. I think it’s important to be consulted with a CML specialist, at least to make sure that all these conditions are accomplished.

We know that some patients may not have a baseline pCR, which may be a problem; mainly the patients who never really have pCR detectable. We know there is a very small percentage of patients that exist in the community where they have a negative pCR because it’s not really the classical one that we detect. And in those patients, it’s maybe not safe to discontinue because you are not going to be able to follow the patient after discontinuation. So, in general, although this situation may be a little complicated, very unusual, it is always important to at least have some kind of communication between the doctor, the local oncologist, or even the patient to make sure that when someone decides to discontinue this drug, it can be done in a safe and effective manner.

Kendra Sweet, MD: The EURO-SKI trial was a large study that was done in Europe. I think it was 11 European countries that were involved in this clinical trial. They enrolled 821 patients, and 750 of those patients were evaluable for molecular relapse-free survival. So, in this study, patients were required to have achieved an MR 4.0 and maintain that response for a minimum of 1 year prior to discontinuation of therapy. As we’ve seen with a number of other discontinuation trials, the majority of patients who lose their molecular response did so pretty early on. At 6 months, it was around 60% to 62% of patients who were still free of molecular relapse, and that number declined slowly after that. But by 2 years, it was 52% of patients who were still free of a molecular relapse. In this study, the definition of molecular relapse was loss of MMR.

The comforting thing about this study, along with many of the other discontinuation trials, is that in the patients who did relapse, they were restarted on their prior TKI and nearly everybody regained their prior level of molecular response, suggesting that there’s not a lot of harm in attempting discontinuation of therapy as long as we’re monitoring these patients closely. But this is, by far, the largest TKI discontinuation trial that has been done and definitely supports the data from prior studies, making, I think, everybody feel more comfortable with the concept and bringing it more into the mainstream.

Transcript Edited for Clarity