CML-110: Predictors of Durable Treatment-Free Remission After Frontline or Second-Line Nilotinib Treatment in Patients with Chronic Phase Chronic Myeloid Leukemia

Abstract

Context While some patients with chronic myeloid leukemia in chronic phase who maintain a deep molecular response (DMR) with tyrosine kinase inhibitors (TKIs) can discontinue treatment and achieve treatment-free remission (TFR), variables that reliably predict TFR are unknown. Objective Identify clinical predictors of TFR using pooled data from long-term follow-up studies (ENESTfreedom and ENESTop) of TFR following front- or second-line nilotinib. Patients In ENESTfreedom, patients with MR4.5 and ≥2 years of frontline nilotinib were enrolled and entered a 1-year nilotinib consolidation phase, after which those who maintained DMR in 4 quarterly assessments could enter the TFR phase (n=190). In ENESTop, patients with >4 weeks of imatinib followed by ≥2 years of nilotinib (≥3 years of total TKI therapy) who achieved MR4.5 on nilotinib were enrolled; patients entered a 1-year nilotinib consolidation phase, and those with no loss of MR4.5 subsequently entered the TFR phase (n=126). Main outcome measures Data from all patients who entered the TFR phases of ENESTfreedom and ENESTop were pooled. Univariate and multivariate analyses were conducted to identify predictors of durable TFR (i.e., remaining in the TFR phase with MR4.5 at 24 weeks). Variables assessed as predictors were age, sex, time since MR4.5 achievement until TFR phase entry, and duration of nilotinib prior to TFR. Results Among all patients who entered the TFR phases of ENESTfreedom and ENESTop, 180/316 achieved durable TFR at 24 weeks. In the univariate analysis, time since MR4.5 achievement until TFR phase entry (P=0.0025) and duration of nilotinib prior to TFR phase entry (P=0.0008) were significantly associated with durable TFR. Duration of nilotinib prior to TFR phase entry was the only significant predictor (P=0.0333) found in the multivariate analysis, with a 1-month increase in the duration of nilotinib treatment being associated with a 3.6% increase in the odds of durable TFR. Conclusions Pooled analyses suggest that durable TFR at 24 weeks was associated with duration of nilotinib prior to TFR. These data could help physicians with patients who are considering attempting TFR. Study sponsored by Novartis Pharmaceuticals Corporation. This abstract was accepted and previously published at the 61st ASH® Annual Meeting and Exposition.