Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina

Abstract

Key Points• Chinese patients with newly diagnosed CML-CP achieved higher rates of MMR with nilotinib vs imatinib.• Nilotinib was well tolerated, and no new safety signals were observed.Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently the standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP).In this study, we present results of the ENESTchina (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-China) that was conducted to investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a Chinese population. ENESTchina met its primary end point with a statistically significant higher rate of major molecular response (MMR; BCR-ABL1 £0.1% on the International Scale) at 12 months in the nilotinib arm vs the imatinib arm (52.2% vs 27.8%; P < .0001), and MMR rates remained higher with nilotinib vs imatinib throughout the follow-up period. Rates of complete cytogenetic response (0% Philadelphia chromosome-positive [Ph1] metaphases by standard cytogenetics) were comparable and ‡80% by 24 months in both arms. The estimated rate of freedom from progression to accelerated phase/blast crisis at 24 months was 95.4% in each arm. The safety profiles of both drugs were similar to those from previous studies. In conclusion, rates of MMR at 12 months were superior with nilotinib vs imatinib in Chinese patients with newly diagnosed Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01275196. (Blood. 2015;125(18):2771-2778

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

“…Other efficacy and safety results were generally similar to those from ENESTnd and other studies of frontline nilotinib in patients with CML‐CP (Rosti et al , 2009; Saglio et al , 2010; Kantarjian et al , 2011; Wang et al , 2015; Hochhaus et al , 2016b). Very few progressions to AP/BC were reported during or after discontinuation of study treatment, and very few patients died due to CML.…”

“…Notably, despite the opportunity for dose optimization in ENESTxtnd, the rates of discontinuation of study treatment and discontinuation due to AEs were similar to those in the nilotinib 300‐mg twice‐daily arm of ENESTnd (by the 2‐year data cut‐off, 26% and 9%, respectively) (Kantarjian et al , 2011), as well as those in ENEST1st (by the end of the 2‐year study, 19·1% and 10·7%, respectively) (Hochhaus et al , 2016b). As in prior studies, most non‐haematological AEs were grade 1/2 (Rosti et al , 2009; Saglio et al , 2010; Kantarjian et al , 2011; Wang et al , 2015; Hochhaus et al , 2016b). Approximately half of patients had dose interruptions or adjustments due to AEs and overall, among patients with dose reductions, most of those who attempted to re‐escalate were successful.…”

Is there a best TKI for chronic phase CML?

“…17 However, rates of both CCyR (84% vs 87%) and freedom from progression (95% each) were similar at 24 months.…”

“…The experimental arms have included higher doses of imatinib, imatinib plus interferon, or one of the second generation TKIs. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] Whether 400 mg daily is the optimal starting dose for imatinib is not clear; some trials, but not all, have shown superior achievement of major molecular responses (MMRs) with 600 or 800 mg daily. [6][7][8][9][10][11] Notably, however, there have been no randomized comparisons of the second generation TKIs against each other.…”

Philadelphia-Positive B-Acute Lymphoblastic Leukemia: Does it Differ from Philadelphia-Negative One in Egyptian Populations?

“…This finding compared to older studies prior to use of Imatinib in Ph+ ALL showed that Ph+ patients had poorer outcome. [7][8][9] International Journal of Hematology and Oncology Concerning Molecular response (MR), in the present study after receiving chemotherapy accompanied with Imatinib, minor BCR-ABL fusion gene was expressed in mRNA of patient leukocyte (Mean ± SD = 0.006± 0.006), with a 3 log reduction from baseline ratio. This is in accordance with the results previously reported that when Imatinib is added to induction therapy, minor BCR-ABL , mRNA was reduced at least 1 log from baseline after the first induction therapy.…”