Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial.

The ENESTfreedom trial assessed the feasibility of treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase (CML-CP) following frontline nilotinib treatment. Results for long-term outcomes after a 5-year follow-up are presented herein. Patients who had received ≥2 years of frontline nilotinib therapy and achieved MR4.5 underwent a 1-year nilotinib treatment consolidation phase before attempting TFR. At the 5-year data cut-off, 81/190 patients entering the TFR phase (42.6%) were still in TFR, with 76 (40.0%) in MR4.5. Patients who lost major molecular response (MMR) entered a treatment re-initiation phase; 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. The Kaplan-Meier estimated treatment-free survival rate at 5 years was 48.2%. No disease progression or CML-related deaths were reported. Whereas the incidence of adverse events (AEs) declined from 96 weeks following the start of TFR, an increase in AE frequency was observed for patients in the treatment re-initiation phase. Low Sokal risk score, BCR-ABL1IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates. Overall, these results support the efficacy and safety of attempting TFR following upfront nilotinib therapy of >3 years in patients with CML-CP.

Relevance of renin expression by real-time PCR in acute myeloid leukemia.

The search for useful molecular markers in the diagnosis of AML and in the follow-up of minimal residual disease (MRD) has been the focus of many recent studies. Previous research showed that, while normal bone marrow cells lack expression of renin, myeloid blasts have been reported to do so. The aim was to study the expression of the renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. This study analysed 76 samples from patients with AML, with follow-up of positive patients. Thirty-one patients (41%) were positive for renin gene expression at diagnosis. All renin-positive patients at diagnosis showed no expression during complete remission (CR), but expression recurred in those experiencing relapse and persisted when the disease was refractory to treatment. Although the results suggest that the sub-group of renin-positive AML patients might have a worse outcome and a higher relapse rate (at 5 years, the projected rate of disease-free survival was 18.5 +/- 9.8% for renin-positive and 23.5 +/- 8.8% for renin-negative patients), no significant differences were found. It is believed that further studies should aim to validate whether such a difference exists, using a much larger and homogeneus group of patients.