Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Single US Center Experience

Imatinib (IM) can be safely discontinued in patients with chronic myeloid leukemia (CML) with sustained complete molecular remission. Previous publications from France and Australia have shown that overall 40% maintain MMR or MR5 for up to 5 years after IM is stopped. We report single US center experience with tyrosine kinase inhibitor (TKI) discontinuation. Between 06/2010 and 7/2015, 22 patients with CML in chronic (CP, n=19), accelerated (AP, n=2) and lymphoid blast phase (LBP, n=1) discontinued IM (n=17), dasatinib (DAS, n=3) or bosutinib (BOS, n=2), and were monitored by qPCR for BCR-ABL1 monthly for the first 3 months, quarterly for the following 2 years and then bi-annually. TKI was restarted in case of confirmed loss of MMR on a repeat qPCR. Reason for TKI discontinuation was predominantly driven by patients' request and TKI intolerance. Median age was 66 (range, 21-84). The 3 who discontinued DAS had IM-resistant (loss of CCyR; n=1), IM-intolerant CP (n=1), or received DAS as first-line agent (n=1).  BOS was discontinued for IM-intolerant CP (n=1), or while in CR2 in a patient with LBP that transformed from IM resistant CP and relapsed following chemotherapy (HCVAD). Median duration of TKI therapy pre-discontinuation for the entire cohort was 89 months (range, 26-106). Three patients are not evaluable due to short follow-up (TKI stopped between 5/2015 and 7/2015).

With a median follow-up of 40 months (range, 8-60), 7 (41%, 6 CP and 1 AP), all previously on IM lost MMR a median of 3 months (range, 3-24) after TKI was stopped and restarted IM. Loss of CHR occurred 13 months after loss of MMR in 1 patient who elected not to restart IM at the time MMR was lost, due to complications from cardiac transplant rejection. All 7 achieved MMR following restart of IM. Median duration of TKI therapy pre-discontinuation for these 7 patients was 60 months (range, 48-98). 12 patients (59%, 10 CP, 1 AP, 1 LBP) remain off TKI and have not lost MMR, 8 with continuously undetectable BCR-ABL1; and 4 had 1-2 transient detectable BCR-ABL1 at MR4 levels. Median duration of TKI therapy pre-discontinuation for these 12 patients was 87 months (range, 26-106). Loss of MMR-free survival is depicted in the Figure. We conclude that, similar to previous reports, TKI can be safely discontinued in patients with CML without reappearance of BCR-ABL1 in 50-60%.