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Author Notes:

carlo.gambacorti@unimib.it

The study was created/designed by C.G.P., H.J.K., and J.E.C. C.G.P., H.M.K., D.W.K., H.J.K., A.G.T., T.H.B., and J.E.C. collected and assembled the data. C.G.P., H.M.K., D.W.K., H.J.K., A.G.T., T.H.B., E.M., N.B.B., M.S., K.T., E.L., and J.E.C. provided analysis and/or interpretation of the data and provided study materials and/or enrolled patients in the study. E.L. performed statistical analyses. All authors assisted in the writing and/or critical review of the manuscript, and all authors approved the final version of the manuscript for submission.

The authors acknowledge all of the participating patients and their families as well as the global network of investigators, research nurses, study coordinators, and operations staff. The authors are also very grateful to Virginia Kelly, MD, Nadine Besson, MSc, and Athena Countouriotis, MD, for their contributions to this study. Editorial and medical writing support was provided by Simon Slater, PhD, and Cynthia Gobbel, PhD, CMPP, of Complete Healthcare Communications, Inc., and was funded by Pfizer.

Conflict of interest: C.G.P. has received research funding from Pfizer and consultancy or other fees from Pfizer and Bristol-Myers Squibb; H.M.K. has received research funding from Pfizer; D.W.K. has received research funding, consultancy and other fees, and served as a member on the board of directors or advisory committees for Bristol-Myers Squibb, Ilyang Co, Novartis, and Pfizer; H.J.K. has received research funding, consultancy and other fees, and served as a member on the board of directors or advisory committees for Pfizer; A.G.T. has served as a consultant/advisor, participated on the Speakers’ bureau, and received honoraria from Bristol-Myers Squibb and Novartis; T.H.B. has received research funding from Novartis and Pfizer, consultancy and other fees from Ariad, Bristol-Myers Squibb, Novartis, and Pfizer, and has received patent royalties (use of imatinib and hypusination inhibitors); E.M., N.B.B., M.S., K.T., and E.L. are employees of Pfizer, and N.B. and V.K. are former employees of Pfizer; J.E.C. has received research funding and consultancy and other fees from Ariad, Bristol-Myers Squibb, Novartis, and Pfizer, and research funding from Teva.

Subject:

Research Funding:

This study was sponsored by Wyeth Research, which was acquired by Pfizer in October 2009. Programming support was provided by ICON plc.

Keywords:

  • bosutinib
  • long-term efficacy
  • leukemia
  • treatment failure
  • chronic myeloid leukemia
  • blast-phase
  • acute lymphoblastic leukemia
  • treatment duration
  • hematologic resonse

Long‐term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors

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Journal Title:

AMERICAN JOURNAL OF HEMATOLOGY

Volume:

Volume 90, Number 9

Publisher:

, Pages 755-768

Type of Work:

Article | Final Publisher PDF

Abstract:

Long‐term efficacy and safety of bosutinib (≥4 years follow‐up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated‐phase [AP, n = 79] chronic myeloid leukemia [CML], blast‐phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1–88.6), 2.8 (0.03–55.9), 0.97 (0.3–89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan‐Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib‐related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge‐to‐transplant role in BP patients); toxicity was manageable.

Copyright information:

© 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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