@article{b2bd22cb8da143678b4143e08f067571,
title = "Treatment-free remission in patients with chronic myeloid leukemia following the discontinuation of tyrosine kinase inhibitors",
abstract = "Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, and conducted a multivariate analysis for factors associated with loss of MMR. Two-hundred and eighty-four patients were analyzed; 199 patients (70%) electively discontinued TKIs. At a median follow-up of 36 months (95% confidence interval, 32–40) after TKI discontinuation, 53 patients (19%) lost MMR. The estimated 5-year TFR rate was 79%. All but one patient regained MMR after resuming therapy. The estimated 5-year TFR rates were higher with MR4 and MR4.5 ≥5 years, compared with MR4 <5 years (87% vs. 92% vs. 64%; p <.0001). By multivariate analysis, only the duration of MR4 or MR4.5 ≥5 years before stopping treatment was associated with a lower risk of loss of MMR. In summary, TFR is safe and feasible in patients with Ph-positive CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years is correlated with a better outcome.",
author = "Haddad, {Fadi G.} and Koji Sasaki and Issa, {Ghayas C.} and Guillermo Garcia-Manero and Farhad Ravandi and Tapan Kadia and Jorge Cortes and Marina Konopleva and Naveen Pemmaraju and Yesid Alvarado and Musa Yilmaz and Gautam Borthakur and Courtney DiNardo and Nitin Jain and Naval Daver and Short, {Nicholas J.} and Elias Jabbour and Hagop Kantarjian",
note = "Funding Information: This work is supported in part by the MD Anderson Cancer Center Leukemia SPORE CA100632, the Cancer Center Support Grant (CCSG) P30CA016672, and the Charif Souki Cancer Research Grant. Funding Information: Koji Sasaki received research funding and consultancy fees from Novartis; and is on the advisory board for Daiichi‐Sankyo and Pfizer. Ghayas C. Issa received research funding from Celgene, Kura Oncology, Syndax, and Novartis; and consultancy fees from Novartis and Kura Oncology. Jorge Cortes received research support from Novartis, Takeda, Pfizer, and Sun Pharma; and consultancy fees from Novartis, Takeda, Incyte, Sun Pharma, and Pfizer. Marina Konopleva received research funding from AbbVie, Genentech, F. Hoffman La‐Roche, Eli Lilly, Cellectis, Calithera, Ablynx, Stemline Therapeutics, Agios, Ascentage, AstraZeneca, Rafael Pharmaceutical, Sanofi, Forty‐Seven; received consultancy fees or honoraria from AbbVie, Genentech, F. Hoffman La‐Roche, Stemline Therapeutics, Amgen, Forty‐Seven, Kisoji, Janssen; is on the advisory board for Stemline Therapeutics, F. Hoffman La‐Roche, Janssen; and has stocks or royalties in Reata Pharmaceutical, Novartis, and Eli Lilly. Naval Daver received research funding from Daiichi‐Sankyo, Bristol‐Myers Squibb, Pfizer, Gilead, Sevier, Genentech, Astellas, Daiichi‐Sankyo, Abbvie, Hanmi, Trovagene, FATE therapeutics, Amgen, Novimmune, Glycomimetics, Trillium, and ImmunoGen; and served in a consulting or advisory role for Daiichi‐Sankyo, Bristol‐Myers Squibb, Arog, Pfizer, Novartis, Jazz, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen, Shattuck labs, and Agios. Elias Jabbour received research grants from Abbvie, adaptive biotechnologies, Amgen, Pfizer, and Takeda; and consultancy fees from Abbvie, adaptive biotechnologies, Amgen, BMS, Genentech, Incyte, Novartis, Pfizer, and Takeda. Hagop Kantarjian received research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi‐Sankyo, Immunogen, Jazz, Novartis, Pfizer; and honoraria from AbbVie, Amgen, Aptitude Health, Ascentage, Astellas Health, Astra Zeneca, Ipsen, Pharmaceuticals, KAHR Medical Ltd, NOVA Research, Novartis, Pfizer, Precision Biosciences, Taiho Pharmaceutical Canada. Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",
year = "2022",
month = jul,
doi = "10.1002/ajh.26550",
language = "English (US)",
volume = "97",
pages = "856--864",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "7",
}