Vivian G. Oehler, MD, discusses the important aspects of TKI discontinuation and the patient factors that would warrant such an approach.
Vivian G. Oehler, MD
Even if a patient with chronic myeloid leukemia (CML) qualifies for tyrosine kinase inhibitor (TKI) discontinuation, it does not mean they are out of the woods, explained Vivian G. Oehler, MD, adding that monitoring becomes even more important in this context.
“Monitoring is critical for patients in chronic phase CML. We know that about 50% of patients who stop their TKI will have a molecular relapse that requires restarting therapy,” said Oehler. “Eighty-five percent of that group will relapse within the first 6 months, but we also know that late relapses can occur. Given the wonderful prognosis that patients with CML might have, we want to make sure not to miss them.”
In an interview during the 2019 OncLive® State of the Science Summit™ on Hematologic Malignancies, Oehler, an associate member of the Fred Hutchinson Cancer Research Center, associate professor of medicine, Division of Hematology, University of Washington School of Medicine, discussed the important aspects of TKI discontinuation and the patient factors that would warrant such an approach.
OncLive®: What are some of the factors you consider when deciding if TKI discontinuation is appropriate or not?
Oehler: Now that patients with CML have normal life expectancies, the question becomes, “Are there strategies we can use to improve quality of life for those who have excellent molecular responses, [defined by] deep and major molecular responses?” For most of the studies that have been run abroad and in the United States, the general criteria for TKI cessation includes being on a TKI for at least 3 years and having a deep molecular response of 2 years or longer. However, the ongoing EURO-SKI study only requires a deep molecular response at MR4 for less than 1 year. We also want to have a transcript that we know has been measured accurately over time, as with a PTEN transcript.
How do you approach these conversations with patients? Are they skeptical of discontinuing therapy?
It's probably one of the most common consults I get. I've found that patients who have been on TKIs the longest and remember the “old days” of CML treatment have been a little more reluctant to stop therapy. In the United States, we really didn't have any clinical trials for these patients, so we were stopping treatment on our own with close monitoring [which is in line with] what they were doing abroad.
On the other hand, we have patients who are very eager to [discontinue treatment]. I have several young patients who might not have completed family planning. For them, getting a deep response so that they can complete all of that is important. The patients who come in are quite interested. Although, there are patients out there who are curious about why it might be possible for them to remain off therapy. At this point, although we think the immune microenvironment has something to do with it, our understanding of that remains unclear.
What are some of the remaining challenges in the field?
Dasatinib (Sprycel) is a great drug to use. It’s well tolerated, but pleural effusions can become a bit of an issue over time. Therefore, I’m looking very closely at ongoing studies, in particular a pilot study at The University of Texas MD Anderson Cancer Center, which is looking at dose reductions as a strategy. Many of us already do that in clinic, but to see those data come out showing that patient responses are just as good, if not better, because they can remain on therapy [would be great]. Additionally, we know the OPTIM-Dasatinib study is looking at targeting dasatinib to a pharmacokinetic level to minimize toxicity, but still keep patients on track. The same is true for some of the other TKIs we're using.