@article{3043181be2e74ced928710182de15cc5,
title = "Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis",
abstract = "ENESTnext (NCT01227577) was a single-arm, multicenter trial evaluating the rate of deep molecular response by 2 years in patients with newly diagnosed (within 6 months) chronic myeloid leukemia in chronic phase (CML-CP) treated with nilotinib 300 mg twice daily. Among 128 enrolled patients, 94 (73%) achieved major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) and 34 (27%) achieved confirmed MR4.5 (BCR-ABL1IS ≤0.0032% detectable or undetectable; primary endpoint) by 2 years. Three-month BCR-ABL1 levels were predictive of later responses. In exploratory analyses, digital polymerase chain reaction (PCR) detected BCR-ABL1 in 39.4% of samples from patients with confirmed MR4.5 and identified further decreases in BCR-ABL1 with continued nilotinib. Safety results, including cardiovascular events, were consistent with those in other nilotinib trials. These results further substantiate the molecular response rates associated with frontline nilotinib therapy and demonstrate the feasibility of monitoring very low BCR-ABL1 transcript levels using digital PCR.",
keywords = "BCR-ABL1, chronic myeloid leukemia, deep molecular response, digital PCR, nilotinib",
author = "Berdeja, {Jesus G.} and Heinrich, {Michael C.} and Dakhil, {Shaker R.} and Goldberg, {Stuart L.} and Martha Wadleigh and Philip Kuriakose and Jorge Cortes and Jerald Radich and Bret Helton and David Rizzieri and Carole Paley and Ilva Dautaj and Mauro, {Michael J.}",
note = "Funding Information: The authors declare the following relationships: J G Berdeja: reports research funding from Abbvie, Amgen, Bluebird, BMS, Celgene, Genentech, Glenmark, Janssen, Novartis, Poseida, Sanofi, Takeda, and Teva; consulting role for BMS, Celgene, CRISPR Therapeutics, Karyopharm, Kite Pharma Inc, Servier, and Takeda; M C Heinrich: reports research funding from Novartis, Pfizer, BMS, MolecularMD; consulting or advisory role for Novartis, Ariad, Blueprint, Pfizer, and MolecularMD; equity ownership in MolecularMD; honoraria from Novartis and Pfizer; patents and royalties from Novartis; S R Dakhil: has nothing to disclose; S L Goldberg: reports research funding from Ariad, BMS, Novartis, and Pfizer; participation in a speakers bureau for Ariad, BMS, and Novartis; M Wadleigh: has nothing to disclose; P Kuriakose: has nothing to disclose; J Cortes: reports research funding from Ariad, BMS, Novartis, Pfizer, and Teva; consulting or advisory role for Ariad, BMS, Novartis, and Pfizer; J Radich: reports research funding from Novartis; consulting or advisory role for Novartis; B Helton: has nothing to disclose; D Rizzieri: reports participation in a speakers bureau for Novartis; C Paley: is employed by Novartis; I Dautaj: was employed by Novartis at the time the study was conducted; M J Mauro: reports research funding from Novartis; consulting or advisory role for Novartis, BMS, Ariad, and Pfizer. The authors thank Ghulam Warsi, PhD, formerly of Novartis Pharmaceuticals Corporation, for statistical support of this study, Das Purkayastha, PhD, of Novartis Pharmaceuticals Corporation for statistical review of the manuscript, and Jenna Voutsinas, MPH, of the Fred Hutchinson Cancer Research Center for statistical support on the digital PCR analyses. The authors also thank Joy Loh, PhD, and Jonathan Morgan, PhD, formerly of ArticulateScience LLC for medical editorial assistance. Editorial assistance was funded by Novartis Pharmaceuticals Corporation. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 The Author(s). Published by Informa UK Limited, trading as Taylor &Francis Group.",
year = "2019",
month = aug,
day = "24",
doi = "10.1080/10428194.2019.1590569",
language = "English (US)",
volume = "60",
pages = "2384--2393",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "10",
}
