Treatment-Free Remission in Chronic Phase Chronic Myeloid Leukemia After Nilotinib De-Escalation. 96-Week Update of the DANTE Study

Treatment-free remission (TFR) in chronic myeloid leukemia (CML) can be considered for patients in sustained deep molecular response (DMR) who can discontinue tyrosine kinase inhibitors (TKIs) while maintaining responses. Studies suggest that TKI de-escalation before TFR is feasible. This phase II study evaluated nilotinib de-escalation outcomes in adults with CML in chronic phase (CP) treated with first-line nilotinib for ≥ 3 years and in sustained DMR for ≥ 1 year. The study had four phases: screening, de-escalation (week 0–48), TFR (week 48–144) and follow-up. During de-escalation, patients received nilotinib 300 mg once daily, and those with sustained DMR entered TFR and discontinued nilotinib. Patients with major molecular response (MMR) but without sustained DMR continued nilotinib. At the data cut-off, 107 patients entered, and 98 (91.6%) completed de-escalation. TFR was entered by 90 patients (84.1%) with sustained DMR. At 96 weeks, 71/107 patients (66.4%) were in full TFR; 64/90 patients (71.1%) who entered TFR remained in ≥ MMR, and the median time-to-loss of MMR was not reached. During TFR, adverse events occurred in 64 patients (71.1%), including one serious event (pneumonia). Our data suggest that the de-escalation of nilotinib before a TFR attempt in CML-CP patients with sustained DMR can be a successful dose optimization strategy.