@article{82d82e52bca8417ab59cc2abfa88326f,
title = "Molecular response in newly diagnosed chronic-phase chronic myeloid leukemia: prediction modeling and pathway analysis",
abstract = "Tyrosine kinase inhibitor therapy revolutionized chronic myeloid leukemia treatment and showed how targeted therapy and molecular monitoring could be used to substantially improve survival outcomes. We used chronic myeloid leukemia as a model to understand a critical question: why do some patients have an excellent response to therapy, while others have a poor response? We studied gene expression in whole blood samples from 112 patients from a large phase III randomized trial (clinicaltrials gov. Identifier: NCT00471497), dichotomizing cases into good responders (BCR::ABL1 ≤10% on the International Scale by 3 and 6 months and ≤0.1% by 12 months) and poor responders (failure to meet these criteria). Predictive models based on gene expression demonstrated the best performance (area under the curve =0.76, standard deviation =0.07). All of the top 20 pathways overexpressed in good responders involved immune regulation, a finding validated in an independent data set. This study emphasizes the importance of pretreatment adaptive immune response in treatment efficacy and suggests biological pathways that can be targeted to improve response.",
author = "Radich, {Jerald P.} and Matthew Wall and Susan Branford and Campbell, {Catarina D.} and Shalini Chaturvedi and DeAngelo, {Daniel J.} and Deininger, {Michael W.} and Justin Guinney and Andreas Hochhaus and Hughes, {Timothy P.} and Kantarjian, {Hagop M.} and Larson, {Richard A.} and Sai Li and Rodrigo Maegawa and Kaushal Mishra and Vanessa Obourn and Javier Pinilla-Ibarz and Das Purkayastha and Islam Sadek and Giuseppe Saglio and Alok Shrestha and White, {Brian S.} and Druker, {Brian J.}",
note = "Funding Information: All authors received non-financial support (assistance with manuscript preparation from ScientificPathways, Inc, which received funding from Novartis). JPR received research funding from TwinStrand Biosciences and Novartis. MW, JG, and BSW were supported by a contract with Novartis for this study. SB is a member of the advisory boards of Qiagen, No-vartis, and Cepheid and has received honoraria from Qiagen, Novartis, Bristol Myers Squibb, and Cepheid, as well as research support from Novartis. SB is also supported by the National Health and Medical Research Council of Australia APP1027531 and APP1104425, the Ray and Shirl Norman Cancer Research Trust, and the Royal Adelaide Hospital Research Foundation. RAL has acted as a consultant or advisor to Novartis, Amgen, Ariad/Takeda, Astellas, Celgene/Bristol Myers Squibb, CVS/Caremark, Epizyme, and MorphoSys and has received clinical research support from Novartis, Astel-las, Celgene, Cellectis, Daiichi Sankyo, Forty Seven, and Ra-fael Pharmaceuticals and royalties from UpToDate. HMK received honoraria from AbbVie, Amgen, DaiichiSankyo, No-vartis, Pfizer, Adaptive Biotechnologies, Aptitude Health, Bio-Ascend, Delta Fly, Janssen Global, Oxford Biomedical, and Takeda, received grants from Ascentage, Bristol Myers Squibb, DaiichiSankyo, Immunogen, Jazz, Novartis, Pfizer, and Sanofi, and acted as a member of an advisory board for Actinium. MD is a paid consultant for Blueprint, Fusion Pharma, Takeda, Novartis, Incyte, Sangamo, SPARC, Pfizer, Medscape, and Dispersol, received research funding from Blueprint, Takeda, Novartis, Incyte, LLS, Pfizer, and SPARC, and participated as a member of advisory boards for Blueprint, Takeda, Incyte, and Sangamo. JP-I received personal fees from Takeda, AbbVie, Janssen, Novartis, Gilead, and TEVA. DJD received honoraria from Amgen, Autolus, Agios, Blueprint, Forty Seven, Incyte, Jazz, Kite, Novartis, Pfizer, Servier, and Takeda, and research support from AbbVie, Gly-coMimetics, Novartis and Blueprint Pharmaceuticals. IS is employed by and has equity in Novartis. SC was employed by Novartis during the conduct of the study. CDC is employed by and is a shareholder of Novartis. RM, SL, KM, DP, AS, and VO are employed by Novartis. BJD Scientific Advisory Board of Aileron Therapeutics, Therapy Architects (ALL-CRON), Cepheid, Vivid Biosciences, Celgene, RUNX1 Research Program, Novartis, Gilead Sciences (inactive) and Monojul (inactive); Scientific Advisory Board and is a stockholder of Aptose Biosciences, Blueprint Medicines, Enliven Therapeutics, Iterion Therapeutics, Third Coast Therapeutics and Publisher Copyright: {\textcopyright}2023 Ferrata Storti Foundation.",
year = "2023",
month = jun,
doi = "10.3324/haematol.2022.281878",
language = "English (US)",
volume = "108",
pages = "1567--1578",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "6",
}