A long-term follow-up of the ENESTfreedom study reported that 96 weeks after stopping treatment, nearly half (48.9%) of patients with chronic myeloid leukemia (CML) who achieved a deep molecular response (DMR) with front-line treatment with nilotinib remained in treatment-free remission (TFR).1
ENESTfreedom was the first study specifically designed to assess the feasibility of TFR in patients with CML who achieved a DMR after front-line treatment with nilotinib. The physicians concluded their findings demonstrated the overall durability of TFR.
Per protocol, after obtaining a molecular response (MR) of MR4.5(defined as BCR-ABL1≤ 0.0032% on the International Scale [BCR-ABL1IS]) with nilotinib administered for more than 2 years, patients transitioned to the TFR phase of the study. Nilotinib was re-initiated if a single assessment showed BCR-ABL1IS> 0.1% (ie, loss of major molecular response [MMR], which is defined as BCR-ABL1IS≤0.1%).
The primary analysis in 190 patients who entered the TFR phase of the study showed 51.6% of patients retained their MMR at 48 weeks after stopping nilotinib; achieving TFR was a determining factor in nilotinib being named the first TKI to get the mention of long-term TFR in its product label.2,3
The median duration of follow-up of the 96-week data cut-off date was 75.9 weeks. At this time, 93 of the 190 patients (48.9%) remained in the TFR phase, 88 (46.3%) re-initiated nilotinib after loss of MMR, and 9 (4.7%) discontinued from the study in the TFR phase.
Five patients who were in the TFR phase at 48 weeks were no longer in this phase at 96 weeks due to a loss of MMR (n = 3) after 48 weeks or loss to follow-up from a decision to discontinue without a loss of MMR.
Treatment-free survival (TFS) at 96 weeks was 50.9% and median TFS was 120 weeks.
Of the 88 patients who were re-challenged with nilotinib due to MMR loss, 87 (98.9%) patients regained MMR and 81 (92%) also regained a MR4.5.
The authors indicate that the TFR rate at 96 weeks as well as the high response rate following nilotinib re-initiation is consistent with results seen in other studies.
Eight deaths were reported at the time of data cut-off — three occurring after the 48-week data cut-off. No death was due to CML or progression to the acute phase or blast crisis. In the follow-up of patients who remained in the TFR phase for more than 48 weeks (n = 100), a decreased frequency of adverse events was reported, with nasopharyngitis (9%) and back pain (5%) being the most frequently-reported ones. Musculoskeletal pain, which occurred early in the TFR phase, also decreased over the 96-week follow up.