At 2 Years, No CML Found in Half of Patients Who Stopped TKI Therapy

Cessation of tyrosine kinase inhibitor (TKI) therapy may be possible in patients with chronic myeloid leukemia (CML) with deep molecular response, according to the results of the Euro-Ski trial (abstract 787) presented this week at the American Society of Hematology (ASH) 58^th Annual Meeting and Exposition, held December 3–6 in San Diego, California.

Of the patients with deep remission who stopped TKI therapy on study, 61% had no evidence of disease recurrence at 6 months, and 52% had no evidence of disease at 18 months.

“With inclusion and relapse criteria less strict than in many previous trials and with decentralized but standardized [polymerase chain reaction]-monitoring, stopping of TKI therapy in a large cohort of CML-patients appears feasible and safe,” said François-Xavier Mahon, MD, PhD, of Bergonié Cancer Center, University of Bordeaux, France, during a press conference.

Many patients with CML treated with TKIs such as imatinib, nilotinib, and dasatinib, can effectively control their disease, and are encouraged to remain on the drugs indefinitely; however, costs and side effects of these treatments have led to research to determine whether or not it would be feasible to discontinue use of TKIs in patients with consistently negative leukemia tests.

The Euro-Ski trial enrolled 821 patients with chronic phase CML from 11 European countries from May 2012 to December 2014. All patients had been treated with imatinib, nilotinib, or dasatinib and were in deep molecular remission for at least 1 year prior to the proposed cessation of TKI therapy. The researchers defined molecular recurrence as BCR-ABL > 0.1% (loss of major molecular response [MMR]) at one time point.

The researchers estimated molecular recurrence-free survival (MRFS) for 755 patients with assessable molecular data. Loss of MMR occurred in 373 patients; 78.3% of those were within the first 6 months. Four deaths in remission occurred.

The median follow-up for all patients was 14.9 months, and the median follow-up for patients without events was 26 months. The MRFS rate was 61% at 6 months (95% CI, 58%–65%), 55% at 12 months (95% CI, 51%–58%), and 50% at 2 years (95% CI, 47%–54%).

Dr. Mahon noted that longer duration of imatinib-therapy prior to TKI cessation correlated to a higher probability of relapse-free survival. According to the abstract, the researchers used prognostic modeling based on 448 patients treated with imatinib. A univariate analysis showed that treatment duration with imatinib and duration of molecular response prior to cessation were significantly associated with MMR status (P < .001). Each additional 1 year of treatment with imatinib increased the odds to stay in MMR at 6 months by 16%.

MRFS at 6 months was 65.5% for patients who had been on imatinib for longer than 5.8 years compared with 42.6% for patients who were on imatinib for 5.8 years or less.

Dr. Mahon concluded that the results of this study are useful and support edits to new European Leukemia Net recommendations.