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Abstract Background Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP‐CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment‐free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence‐free survival (MRFS) after stop according to recommendations. Methods Over a 10‐year period, newly diagnosed CP‐CML patients and treated with first‐line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first‐line treatments. Results From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41–62.19] at 2 years and 43.8% [31.45–56.15] at 5 years. Patients receiving frontline second‐generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others. Conclusion One third of CP‐CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second‐generation TKI frontline were associated with the highest MRFS.

Abstract Purpose To assess the incidence of BCR‐ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP‐CML) patients treated with tyrosine kinase inhibitors (TKIs). Patients and Methods We analyzed characteristics and outcome of 253 CP‐CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first‐line TKI. Results Overall, 80 (32%) patients harbored BCR‐ABL KD mutations. A BCR‐ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP‐BP), and 47%, 29%, 35%, 16% and 26% in patients in CP‐CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively. Overall survival and cumulative incidence of CML‐related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P‐loop vs non‐T315I non‐P‐loop) (P

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome.

In chronic myeloid leukemia (CML), cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y−) was compared to 30 Y+ control males diagnosed and treated at the same time in the same institutions. Y− patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and shorter overall survival than Y+ patients. The negative impact of this abnormality was particularly marked when it occurred in a sub-clone (clonal evolution) rather than in all mitoses. These data indicate that loss of the Y chromosome should be taken into account in the prognostic evaluation of chronic myelogenous leukemia patients.