Long-Term Outcomes after Imatinib Mesylate Discontinuation in Chronic Myeloid Leukemia Patients with Undetectable Minimal Residual Disease

Abstract

Background: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. Methods: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥12 months between June 2009 and January 2013. Results: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation. With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. Conclusion: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility.

The Importance of Being Cured: A Chronic Myeloid Leukemia Perspective

“…There are several similarities between the retrospective cohort study conducted by Yhim et al [6] and previous prospective clinical trials. In the current analysis, molecular relapse was not observed after 2 years of imatinib discontinuation, allowing for a less stringent follow-up after this time period.…”

“…The retrospective study conducted by Yhim et al [6] and published in this issue of Acta Haematologica is unique because it sheds light on the issue of treatment discontinuation outside of a prospective clinical trial.…”

“…All in all, the results of the retrospective cohort study by Yhim et al [6] and of previous clinical trials suggest that standardization of the depth of molecular response at discontinuation is necessary and that the optimal UMRD levels making patients eligible for treatment discontinuation should be further validated.…”

“…Finally, it seems that future clinical trials will probably use sustained molecular response as their molecular end point, indicating that the maintenance of a major molecular response, and not necessarily a complete molecular response, can be a harbinger for treatment-free remission [6] . This might further enrich our understanding of the Importance of Being Cured in CML.…”

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells

“…Recent development of tyrosine kinase inhibitors (TKIs) have changed the prognosis of chronic phase CML from a life threatening disease into a treatable chronic disease with substantially increased survival. 34 However, some patients develop resistant mutant clones 56 , and there are a substantial number of cases of recurrence of CML upon TKI withdrawal 7, 8, 9 . Various mechanisms have been proposed to better understand leukemia stem cell (LSC) populations that are responsible for recurrence or relapse.…”