Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study

PURPOSE: ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis. METHODS: Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR(4.5) [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1(IS))], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1(IS) ≤ 0.1%). RESULTS: Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR(4.5) by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR(4.5) during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR(4.5) during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR(4.5), MR(4) (BCR-ABL1(IS) ≤ 0.01%) but not MR(4.5), and MMR but not MR(4) at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes. CONCLUSIONS: These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.