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Ponatinib evaluation and safety in real-life chronic myelogenous leukemia patients failing more than two tyrosine kinase inhibitors: the PEARL observational study.
- Source :
-
Experimental hematology [Exp Hematol] 2018 Nov; Vol. 67, pp. 41-48. Date of Electronic Publication: 2018 Sep 05. - Publication Year :
- 2018
-
Abstract
- Ponatinib represents a remarkable progress in the treatment of heavily pretreated chronic myelogenous leukemia (CML) and de novo Philadelphia chromosome-positive ALL patients despite significant toxicity in clinical trials. To date, "real-life" data remain few and the use of ponatinib in this setting and its consequences remain mostly unknown. We report, within a national observational study, the use of ponatinib in unselected CML patients who had previously failed ≥2 lines of tyrosine kinase inhibitor (TKI) therapy (or one line if an Abelson (ABL) <superscript>T315I</superscript> mutation was identified), in real-life conditions (2013-2014) in a compassionate program. Our analysis has been focused on 48 chronic phase CML patients recorded. With a median follow-up of 26.5 months since ponatinib initiation, the overall survival (OS) rates (80.5% at 3 years) and cumulative incidence of major molecular response (81.8% at 18 months) were similar to those of the phase II study, with no influence of BCR-ABL mutations nor the reason of ponatinib prescription. A specific subanalysis of the preexisting cardiovascular risk factors and events occurring on ponatinib is described. These events occurred after a median time on ponatinib of 5.8 months (excluding hypertension) and were observed in 29/48 patients (47%), even in those already on anti-aggregants/coagulants. The majority were not severe and resolved, but two cases were fatal. Other hematological or nonhematological nonvascular adverse events were similar to those previously described in trials. This observational study reports similar rates of survival, molecular responses, and a slight increase in the cardiovascular toxicity of ponatinib in real-life conditions, prompting improved control of cardiovascular risk factors and selection of patients.<br /> (Copyright © 2018 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents adverse effects
Cardiovascular Diseases chemically induced
Compassionate Use Trials
Drug Resistance, Neoplasm
Female
Genes, abl
Humans
Imidazoles adverse effects
Intention to Treat Analysis
Kaplan-Meier Estimate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology
Male
Middle Aged
Patient Selection
Pragmatic Clinical Trials as Topic
Protein Kinase Inhibitors adverse effects
Pyridazines adverse effects
Survival Analysis
Treatment Failure
Young Adult
Antineoplastic Agents therapeutic use
Imidazoles therapeutic use
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Protein Kinase Inhibitors therapeutic use
Pyridazines therapeutic use
Salvage Therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2399
- Volume :
- 67
- Database :
- MEDLINE
- Journal :
- Experimental hematology
- Publication Type :
- Academic Journal
- Accession number :
- 30195076
- Full Text :
- https://doi.org/10.1016/j.exphem.2018.08.006