STIM Study Examines Sustainability of Complete Molecular Response After Stopping Imatinib in CML

2010 Jan 13, P Wendling

NEW ORLEANS (EGMN) - Complete molecular response can be sustained after stopping imatinib in some patients with chronic myeloid leukemia.

The finding emerged from updated results in the Stopping Imatinib (STIM) study. Although discontinuation is possible even in those treated with single-agent imatinib (Gleevec), lead researcher Dr. Francois-Xavier Mahon recommends discontinuation only in a clinical trial with strict molecular monitoring.

"Is it possible to predict which category of patients may benefit from discontinuation? Not yet, but it is in progress," he said at the annual meeting of the American Society of Hematology. "Male patients with a low Sokal risk and cytotoxic natural killer cells in peripheral blood would be good candidates."

The STIM study was launched in July 2007, after a pilot study in 15 patients showed that most relapses occur during the first 6 months of discontinuation from imatinib - a finding that has held up with a median follow-up of 42.5 months.

STIM has enrolled more than 100 patients, with 21-month follow-up data now available for 69. Overall, 34 patients had been previously treated with interferon and 35 were de novo. They had a median age of 63 years, 26 were male, and prior to enrollment all had complete molecular remission (CMR) for at least 2 years under imatinib treatment.

In all, 40 patients have relapsed (defined as loss of CMR) within the first 6 months of discontinuing imatinib and 1 patient relapsed at month 7, with most relapses occurring in months 2 and 3, said Dr. Mahon of the Université Victor Segalen in Bordeaux, France. The probability of being in CMR at 12 months was 41%.

The probability of being in CMR was not significantly different between the patients who were pretreated with interferon and the de novo patients (47% vs. 34%), with relapses occurring in 53% and 66%, respectively.

The probability of being in CMR was 55% for patients with low risk based on their Sokal score, 36% for those at intermediate risk, and 14% for high-risk patients (P less than .06). Six of seven high-risk patients relapsed, he said.

Despite fewer males in the study, the probability of being in remission at 12 months was significantly higher at 58% for men vs. 30% for women (P = .02). The investigators also observed that the number of mature natural killer cells (mainly CD56 dim cells) at imatinib discontinuation was significantly lower in relapse vs. nonrelapse patients (P = .02).

Dr. Mahon noted that the kinetics of remission may be quite different from one patient to the next, but stressed that all patients were sensitive after imatinib rechallenge and regained CMR.

During a discussion of the study, the investigators were asked whether patients suffer anxiety when stopping imatinib therapy. Dr. Mahon responded that they were happy because side effects disappeared, although it was pointed out by the audience that most side effects should be minimal in patients who were already treated with imatinib for 2 years.

A low risk of progression was observed after 8 years of follow-up in IRIS (International Randomized Study of Interferon and STI571), which helped establish imatinib as the front-line therapy for chronic myeloid leukemia in the chronic phase. At the 8-year data cutoff, 45% of the 553 patients who were randomized to first-line imatinib had discontinued treatment.

Freedom from progression to accelerated phase or blast crisis (AC/BC) was 92% at 8 years. Moreover, the annual rates of progression to AC/BC in years 4-8 were 0.9%, 0.5%, 0%, 0%, and 0.4%, respectively, Dr. Michael Deininger of the Oregon Health and Science University in Portland, reported in a poster (Blood 2009;114:abstract 1126).

Dr. Mahon disclosed a financial relationship with Novartis. 

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