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Recent Data Support TKI Discontinuation in Patients With CML

Brandon Scalea
Published: Monday, Sep 24, 2018

Kendra Sweet, MD
Kendra Sweet, MD
Discontinuation of treatment with a tyrosine kinase inhibitor (TKI) is feasible for a subset of patients with chronic myeloid leukemia (CML), explained Kendra Sweet, MD.

Recent findings from clinical trials have paved the way to determine effective criteria for patients to meet to make them eligible for this option. For example, long-term follow-up data from the Stop Imatinib (STIM1) study indicate that imatinib (Gleevec) can be safely discontinued in patients who have had a sustained deep molecular response and no late molecular recurrence.

Imatinib was prospectively discontinued in 100 patients with CML who had undetectable minimal residual disease (MRD) for at least 2 years. At a median molecular follow-up after treatment discontinuation of 77 months, molecular recurrence-free survival was 43% at 6 months and 38% at 60 months. Sixty-one patients lost undetectable MRD at a median of 2.5 months. None of the patients experienced disease progression.

Additional studies with similar and impactful outcomes include the EURO-SKI and ENESTop trials, Sweet added. In December 2017, the FDA updated the label for nilotinib (Tasigna) with a provision stipulating that patients with Philadelphia chromosome-positive CML in the chronic phase who have received the BCR-ABL TKI for at least 3 years and have achieved specific predetermined criteria may be eligible to stop treatment, based on data from ENESTop and ENESTfreedom. To discontinue therapy, patients must achieve a sustained deep molecular response of MR4.5 (BCR-ABL1 International Scale ≤ 0.0032%).

In an interview during the 2018 OncLive® State of the Science Summit™ on Hematologic Malignancies, Sweet, an assistant member in the Department of Malignant Hematology of Moffitt Cancer Center, shed light on these data regarding treatment discontinuation and how they impact patients with CML.

OncLive: Why is there a focus on discontinuing TKI therapy in CML?

Sweet: There are a number of clinical trials that have been looking at the possibility of discontinuing this class of drugs in a select subset of patients with deep molecular responses who have maintained those responses for a certain period of time. Basically, in every study that’s been done here, the results are strikingly similar. We have consistently seen about 50% of patients relapse, particularly early on. The others are able to maintain what we call a prolonged treatment-free remission. Therefore, in my presentation, I reviewed these different trials that have been completed and published.

Could you highlight some of these trials?

The first discontinuation trial was the STIM1 trial, which was a study done in France starting in 2007. They enrolled 100 patients who were all being treated with imatinib. These patients maintained those deep responses we mentioned earlier for a minimum of 2 years. They then discontinued imatinib and were followed off treatment until molecular relapse. The data from that study are the oldest data we have now. The long-term follow-up was published about 1.5 years ago. There was a 77-month median follow-up time, and 38% of patients remained off treatment. That was the first sort of proof-of-principle study showing that discontinuing therapy for a subset of patients is feasible.

The largest trial in this space done to date is called EURO-SKI. It enrolled 848 patients in Europe on all available TKIs, and 448 of them were on imatinib. Again, we saw very similar data. We saw slightly higher rates of treatment-free remission on that study. This was likely because of less stringent criteria for restarting therapy. That study, again, was able to help define criteria for patients to be eligible to stop therapy.

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