Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported. RESULTS: After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]). CONCLUSIONS: Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML.
Date Issued
2017-04-07
Date Acceptance
2016-12-13
Citation
Cancer, 2017, 123 (15), pp.2875-2880
ISSN
1097-0142
Publisher
Wiley
Start Page
2875
End Page
2880
Journal / Book Title
Cancer
Volume
123
Issue
15
Copyright Statement
© 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Sponsor
Imperial College Trust
Imperial College Trust
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Grant Number
PC3165 01/08/2003
070904JA
RDB05 79560
NF-SI-0611-10275
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
allogeneic stem cell transplantation (allo-SCT)
chronic myeloid leukemia (CML)
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph plus ALL)
ponatinib
threonine to isoleucine mutation at codon 315 (T315I)
ACUTE LYMPHOBLASTIC-LEUKEMIA
MARGINAL STRUCTURAL MODELS
CHRONIC MYELOID-LEUKEMIA
RESISTANT
INHIBITORS
PHASE-2
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
Adult
Aged
Antineoplastic Agents
Blast Crisis
Female
Humans
Imidazoles
Kaplan-Meier Estimate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Multivariate Analysis
Mutation
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Proportional Hazards Models
Pyridazines
Retrospective Studies
Stem Cell Transplantation
Survival Rate
Transplantation, Homologous
Treatment Outcome
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status
Published