Conference Coverage

De-escalation may improve success of TKI cessation


Photo by Patrick Pelletier

Imatinib tablet cut with a pill splitter

MADRID—Results of the DESTINY trial suggest that chronic myeloid leukemia (CML) patients may improve their chances of successfully stopping treatment with tyrosine kinase inhibitors (TKIs) by first reducing the dose they receive.

CML patients in deep molecular response (MR4) at study entry had a low rate of recurrence when they first de-escalated their TKI dose—receiving half the standard dose—for a year and then completely stopped receiving TKI treatment for a year.

The 2-year recurrence-free survival (RFS) rate was 77%, which is better than the RFS in any comparable study to date, according to Richard Clark, MD, of the University of Liverpool in Liverpool, UK, and his colleagues.

Dr Clark presented results from DESTINY at the 22nd Congress of the European Hematology Association (EHA) as abstract S423.

DESTINY included 174 CML patients (98 male, 76 female) in stable major molecular response (MMR).

At study entry, patients had received imatinib (n=148), nilotinib (n=16), or dasatinib (n=10) for a median duration of 6.8 years.

For the first 12 months of the study, patients had their TKI dose reduced to half the standard dose. So they received imatinib at 200 mg daily, dasatinib at 50 mg daily, or nilotinib at 200 mg twice daily. After that, patients stopped treatment completely.

After the first 12 months, molecular recurrence was lower in patients with stable MR4 at study entry than in patients who were not in MR4 (but still in MMR)—2.4% (3/125) and 18.4% (9/49), respectively (P<0.001).

During the following 12 months, in which patients had completely stopped TKI treatment, there were 26 recurrences and 4 withdrawals among the remaining 117 patients who were in MR4 at baseline, as well as 20 recurrences and 4 withdrawals among the 36 patients not in MR4.

So the RFS was 77% among patients in MR4 at baseline and 39% among the patients not in MR4 (P<0.001).

The researchers said the probability of RFS was unrelated to patients’ age, gender, performance status, or the prior TKI they received (imatinib vs second-generation TKI).

All patients with recurrence ultimately returned to deep remissions when they resumed their TKI treatment.

“TKI de-escalation is safe for most CML patients with stable and excellent responses to TKI therapy after some years of treatment and is associated with improvement in symptoms,” Dr Clark said.

“Overall, our findings are better than any other studies worldwide and imply that our unique, gradual withdrawal of treatment might be important. We don’t yet understand why our results are so good, but this is a happy problem to have.”

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