Publication | Closed Access
Treatment-free remission (TFR) following nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTfreedom, ENESTop, ENESTgoal, and ENESTpath.
20
Citations
0
References
2014
Year
T-regulatory CellImmunologyPathologyPharmacotherapyImmunotherapyMahon FxTps7124 BackgroundMyeloid NeoplasiaChronic PhaseHematological MalignancyTranslational MedicineHematologyClinical TrialsTreatment-free RemissionMolecular DiagnosticsRadiation OncologyMolecular ResponseNovel TherapyCancer ResearchHealth SciencesMedicineMolecular MedicineChronic Myeloid LeukemiaClinical TranslationTherapeutic EfficacyTranslational ResearchImmune Checkpoint InhibitorOncology
TPS7124 Background: Approximately 40% of pts who achieve deep, sustained molecular response (MR) on imatinib (IM) are able to successfully maintain TFR (Mahon FX, et al. Lancet Oncol. 2010;11:1029-1035). NIL results in higher rates of deep, sustained MR vs IM and may enable more pts to achieve successful TFR. Four ongoing studies will evaluate the key factors for achieving and sustaining TFR following NIL in pts with CML-CP (Table). Methods: Each study includes a NIL consolidation phase, during which pts undergo frequent molecular monitoring, followed by a TFR phase. In ENESTfreedom and ENESTop, pts with MR4.5 (BCR-ABL ≤ 0.0032% on the international scale [BCR-ABLIS]) on NIL directly enter the 1-y consolidation phase upon enrollment. In ENESTgoal and ENESTpath, pts without deep MR on IM are switched to NIL upon enrollment; after switching to NIL, pts in ENESTgoal who achieve MR4.5 and pts in ENESTpath who complete 2 y of NIL therapy and achieve MR4 (BCR-ABLIS ≤ 0.01%) will be randomized to a 1- or 2-y consolidation phase. Each study protocol defines a required MR level that pts must maintain during the consolidation phase to be eligible for the TFR phase. During the TFR phase of each study, pts must re-initiate therapy if their MR rises above a defined threshold (ie, molecular relapse). The rate and duration of successful TFR on NIL will be evaluated in each study. Clinical trial information: NCT01784068. ENESTfreedom NCT01784068 ENESTop NCT01698905 ENESTgoal NCT01744665 ENESTpath NCT01743989 Planned N 175 117 300 1,058 Treatment prior to enrollment (duration) Frontline NIL (≥ 2 y) Second-line NIL (≥ 3 y total; ≥ 2 y NIL) IM (≥ 1 y) IM (≥ 2 y) Response at enrollment MR4.5 MR4.5 MMR but not MR4.5 Complete cytogenetic response but not MR4 NIL consolidation phase duration 1 y 1 y 1 y or 2 y 1 y or 2 y MR required during NIL consolidation phase to be eligible for TFR phase MR4.5 MR4.5 MR4.5 MR4 Trigger to re-initiate therapy Loss of MMR Loss of MMR or confirmed loss of MR4 Confirmed loss of MR4 Loss of MMR or confirmed loss of MR4 Abbreviations: MMR, major molecular response (BCR-ABLIS ≤ 0.1%).