TKI cessation feasible for patients with CML in deep molecular remission

SAN DIEGO — Patients with chronic myeloid leukemia with a deep molecular response were safely able to stop tyrosine kinase inhibitor therapy with high rates of molecular recurrence–free survival, according to results of the EURO-SKI trial presented at the ASH Annual Meeting and Exposition.

Duration of imatinib therapy of at least 5.8 years prior to stopping therapy was associated with an increased likelihood for molecular recurrence–free survival, results showed.

“Stopping treatment is an emerging goal of CML, because several studies have already demonstrated the possibility of stopping treatment,” Francois-Xavier Mahon, MD, PhD, of Bergonie Cancer Center of University of Bordeaux in France, said during a press conference. “Having a sustained deep molecular response on long-term TKI therapy seems to be necessary priory to treatment-free remission. However, the more precise condition for stopping CML treatments are not yet well defined.”

Mahon and colleagues enrolled 821 patients with chronic phase CML who had no prior TKI failure and who stopped their treatment with imatinib, nilotinib (Tasigna, Novartis) or dasatinib (Sprycel; Bristol-Myers Squibb, Otsuka Pharmaceuticals). Patients were in deep molecular response — or DM⁴, defined as BCR-ABL less than 0.01% on the international scale — for at least 1 year and had received TKI treatment for at least 3 years.

Median follow-up was 14.9 months (range, 0.9-36).

Overall, 755 patients had assessable molecular data for the estimation of molecular recurrence–free survival. Of these patients, 373 lost their major molecular response and four died in remission.

Thus, molecular recurrence–free survival was 61% (95% CI, 58-65) at 6 months, 55% (95% CI, 51-58) at 12 months, 50% (95% CI, 47-54) at 24 months and 47% (95% CI, 43-51) at 36 months.. Most patients were able to regain their deep molecular response, and no patient progressed to advanced disease phase.

Researchers further evaluated data from the 448 patients who had received imatinib. Univariate analysis showed major molecular response status at 6 months was not associated with age, gender, depth of response (MR⁴ vs. MR^4.5), or any variable of the Sokal, EURO, EUTOS or ELTS scores.

However, imatinib treatment duration and MR⁴ duration were significantly associated with major molecular response status at 6 months (P < .001).

Each additional year of imatinib treatment increased the odds of staying in major molecular response at 6 months by 16% (OR = 1.16; 95% CI, 1.08-1.25).

The rate of 6-month molecular recurrence–free survival was 65.5% among patients who had been treated with imatinib for more than 5.8 years, and 42.6% among patients who had been treated for 5.8 years or less, which researchers defined as the optimal cutoff for prior therapy duration.

“Our study would be useful for and support revision of new European Leukemia Net recommendations,” Mahon said. – by Alexandra Todak

Reference:

Mahon F-X, et al. Abstract 787. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: Mahon reports honoraria and research funding from and consultant roles with Ariad, Bristol-Myers Squibb, Novartis and Pfizer. Please see the abstract for a list of all other researchers’ relevant financial disclosures.