STIM1 findings confirm safety of controlled imatinib discontinuation

J Clin Oncol 2016; Advance online publication

medwireNews: Final results of the Stop Imatinib (STIM1) trial confirm that the tyrosine kinase inhibitor (TKI) can be safely discontinued in chronic myeloid leukaemia (CML) patients who achieve a sustained deep molecular response.

The study included 100 patients who agreed to withdrawal of imatinib therapy after achieving undetectable minimal residual disease (UMRD) for at least 2 years, explain Francois-Xavier Mahon, from University Bordeaux in France, and co-authors in the Journal of Clinical Oncology.

After a median of 77 months of follow-up, 61 patients had lost their UMRD status, with molecular recurrence-free survival at 6 months, 18 months and 60 months achieved by 43%, 40% and 38%, respectively.

Molecular recurrence occurred after a median of 2.5 months off-treatment, with 80% of relapses occurring in the first 3 months, 15% between months 4 and 7, and 5% between months 18 and 22.

TKI therapy was restarted in 57 of the patients with molecular recurrence; 55 patients achieved a second UMRD after a median of 4.3 months (range 1.5 to 21.0 months), but two patients failed to do so after treatment was disrupted because of recurrent grade 2 events. Three patients refused to restart TKI therapy and maintained a major molecular response (MMR).

Four patients died from causes other than CML, including two from other types of malignancy, but all of these patients either had UMRD or MMR at their last molecular assessment.

At the last assessment, 37 of the 39 patients free from both molecular recurrence and TKI use had a sustained UMRD and two patients had a 4-log reduction molecular response in ABL–BRC transcripts.

Multivariate analysis showed that likelihood of molecular recurrence was significantly predicted only by a high versus low or intermediate high Sokal risk score (hazard ratio [HR]=2.22) and duration of imatinib therapy at or above the median time of 58.8 months versus a shorter duration (HR=0.54).

Indeed, patients with a low or intermediate Sokal risk score and who had used imatinib for more than 54 months were significantly less likely to experience molecular recurrence than other individuals.

“[I]n this study, Sokal risk score continues to be a strong significant factor associated with early and late [molecular recurrence], suggesting that eradication of the leukemic clone may depend on intrinsic baseline features of the disease”, the authors suggest.

The team notes, however, that both the small study size, and the fact that half the patient group had been previously treated with interferon alpha, “limit the statistical analysis of such predictive factors.”

“In conclusion, the long follow-up of the STIM1 study confirms that [imatinib] discontinuation is safe”, Mahon et al write.

“With respect to the heterogeneous characteristics of the patients, Sokal risk score and [imatinib] duration before treatment discontinuation have to be considered from the perspective of [imatinib] discontinuation.

“These results make treatment-free remission legitimate as a criterion of treatment evaluation in the future.”

By Lynda Williams, Senior medwireNews Reporter

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