Molecular status 36 months after TKI discontinuation in CML is highly predictive for subsequent loss of MMR—final report from AFTER-SKI

Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial

“…STIM1 and TWISTER studies, did not report any MRec after 27 months from imatinib discontinuation with a median follow-up of 6.4 and 8.6 years respectively 13,14 . Since these reports we have identified one MRec 7 years after imatinib discontinuation in the STIM1 study (update currently ongoing) and preliminary results of the EURO-SKI discontinuation trial based on a larger cohort of patients show that cumulative incidence of MRec continues to slowly increase 24 months after TKIs discontinuation 15 with estimated late MRec beyond 36 months ~10% in the AFTER-SKI study 16 . Recently Rousselot et al 17 reported the occurrence of late MRec, defined as loss of MMR after 2 years of TKI cessation, in 9 out of 65 patients with an estimated incidence of 13.8% and a median time from stop to MRec of 3.6 years.…”

“… 13 , 14 Since these reports we have identified one molecular recurrence 7 years after imatinib discontinuation in the STIM1 study (update currently ongoing) and preliminary results of the EURO-SKI discontinuation trial based on a larger cohort of patients show that the cumulative incidence of molecular recurrences continues to increase slowly 24 months after TKI discontinuation, 15 with late molecular recurrences beyond 36 months estimated to occur in approximately 10% of patients in the AFTER-SKI study. 16 Rousselot et al 17 recently reported the occurrence of late molecular recurrences, defined as loss of MMR after 2 years of TKI cessation, in nine out of 65 patients for an estimated incidence of 13.8% and a median time from stopping TKI treatment to molecular recurrence of 3.6 years. With respect to the first report published 2 years ago and in order to identify potential predictive factor(s) of late molecular recurrences, we performed this analysis in the “per-protocol” population (199 patients).…”

Treatment-Free Remission in Chronic Myeloid Leukemia and New Approaches by Targeting Leukemia Stem Cells

“…With 72 months follow-up, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. Interestingly, 1% (1/98) of patients at MR4.0 at 36 months relapsed, yet the risk of relapse for those not at MR4.0 was 85% (11/13), indicating the molecular response at 36 months after TKI discontinuation was highly predictive of molecular relapse (46). The results suggested that the frequency of continued molecular monitoring after three years may depend on the molecular status.…”

Aiming at a Tailored Cure for ERBB2-Positive Metastatic Breast Cancer

“…Moreover, the persistence of detectable circulating disease during anti- ERBB2 treatment appears associated with resistance to the targeted drug . From this perspective, liquid biopsy offers the intriguing possibility of tailoring treatment strategies based on the dynamics of circulating minimal residual disease (MRD), similarly to what is performed in certain hematologic malignant diseases . This could be potentially performed in several ways, including the early identification of patients with curable disease, the interruption of treatment in patients achieving MRD-clearance and/or the modification of treatment in those not achieving MRD clearance.…”