Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily

Abstract

ABSTRACTdifferent therapy "whenever available and applicable". 8

Extending the reach of nilotinib in chronic myeloid leukemia

“…In the Hughes et al study, 4 the authors note adverse events with switch from imatinib to nilotinib were in line with prior phase II studies, including approximately 10% discontinuation for AEs. In the ENESTcmr study, 10 however, with 36 mos of follow up, authors noted that for those patients switching to nilotinib, rates of AEs and related treatment discontinuation were higher in addition to a numerically higher amount of cardiovascular events observed with nilotinib.…”

“…In the ENESTnd trial and forming the basis for the extension study reported herein by Hughes et al, 4 the occurrence of suboptimal response at earlier time points (6 and 12 mos), again reflecting incomplete cytogenetic response, was modest across the study but more common in the imatinib cohort. Suboptimal response at 18 mos, now reflecting incomplete molecular response, was observed much more often (approx.…”

“…In this issue of Haematologica, 4 Timothy Hughes and co-investigators from the ENESTnd trial shed light on an important question arising from this randomized, phase III trial of nilotinib versus imatinib in newly diagnosed Philadelphia-positive (Ph + ) CML in chronic phase. 5 Patients in each of the three arms of the trial (imatinib 400 mg QD, nilotinib 300 mg BID, and nilotinib 400 mg BID) with less than optimal response were offered participation in an extension study.…”

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

“…There are data to suggest that nilotinib dose escalations or reductions, as necessary, can be beneficial for some patients, maximizing both efficacy and tolerability (Rosti et al , 2009; Hughes et al , 2014b; Gugliotta et al , 2015). An ENESTnd extension study evaluated the impact of nilotinib dose escalation in a small cohort of patients ( n  = 19) with suboptimal response or treatment failure on nilotinib 300 mg twice daily; among patients who had not achieved a complete cytogenetic response (CCyR) or MMR at the time of dose escalation, approximately one‐third [33% (2 of 6) and 39% (7 of 18), respectively] achieved CCyR and MMR, respectively, on nilotinib 400 mg twice daily by the data cut‐off (median follow‐up after dose escalation, 19 months) (Hughes et al , 2014b).…”

“…An ENESTnd extension study evaluated the impact of nilotinib dose escalation in a small cohort of patients ( n  = 19) with suboptimal response or treatment failure on nilotinib 300 mg twice daily; among patients who had not achieved a complete cytogenetic response (CCyR) or MMR at the time of dose escalation, approximately one‐third [33% (2 of 6) and 39% (7 of 18), respectively] achieved CCyR and MMR, respectively, on nilotinib 400 mg twice daily by the data cut‐off (median follow‐up after dose escalation, 19 months) (Hughes et al , 2014b). Additionally, an independent study of frontline nilotinib 400 mg twice daily in patients with newly diagnosed CML‐CP demonstrated the feasibility of managing adverse events (AEs) and laboratory abnormalities with nilotinib dose reductions (Rosti et al , 2009; Gugliotta et al , 2015).…”