Late molecular recurrences in patients with chronic myeloid leukemia experiencing treatment-free remission

Abstract

Abstract Treatment-free remission (TFR) is an opportunity for patients with chronic myeloid leukemia (CML). Reported cumulative incidence curves of molecular recurrence (MRec) arbor a 2-phase shape with mainly early events, but also some late events (late MRec [LMRec]). Having discontinued our first patient in 2004, we have access to a prolonged follow-up, enabling us to characterize these late events. Over 15 years, 128 patients from our institution were registered in the Stop Imatinib (STIM; A Study for Tyrosine Kinase Inhibitors Discontinuation [A-STIM]) trial. MRec was defined by the loss of major molecular response (BCR-ABL1IS >0.1%). At the first TFR attempt, patients had been taking a tyrosine kinase inhibitor for a median of 7.1 years and in BCR-ABL1IS ≤0.01% (MR4) for a median of 4 years. The median follow-up of patients in TFR was 6.5 years. The TFR rate was estimated to be 45.6% after 7 years. For 9/65 (14%) patients experiencing MRec, recurrence occurred after 2 years in TFR (median, 3.6 years). The residual rate of MRec after 2 years was estimated to be 18%. The probability of remaining in TFR was 65.4% for patients having experienced fluctuations of their minimal residual disease (MRD) (at least 2 consecutive measurements BCR-ABL1IS >0.0032% or loss of MR4), whereas it was 100% for those with stable MRD (P = .003). After 2 years in TFR, we observed an 18% residual rate of LMRec. These late events represent 14% of all MRec and occur in patients with fluctuating MRD measurements. A long-term molecular follow-up therefore remains mandatory for CML patients in TFR. The A-STIM study was registered at www.clinicaltrials.gov as #NCT02897245.