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Clinical experience with the BCL2‐inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies

Clinical experience with the BCL2‐inhibitor venetoclax in combination therapy for relapsed and... INTRODUCTIONWhile the past decade has improved our understanding of acute myeloid leukemia (AML) as a heterogeneous and clonal hematopoietic malignancy, the outcome of adult patients with AML and other myeloid malignancies remains poor. This is especially true in the relapsed and/or refractory (R/R) adult AML population, where available therapies are limited, responses are inadequate and long‐term survival and cure rates remain <10%. Proceeding to a successful curative stem cell transplant (SCT) in the relapsed setting is possible for only a minor proportion of R/R patients. Encouragingly, targeted therapeutic options for AML patients harboring certain mutations (i.e., IDH2, FLT3) or surface markers (i.e., CD33) now exist, improving upon the standard of care and generating hope for effective small molecule and targeted strategies for additional AML subsets.The antiapoptotic protein B‐cell leukemia/lymphoma‐2 (BCL2) is overexpressed in hematologic malignancies, where it has been implicated in the maintenance and survival of AML cells, therapeutic resistance, and associates with poor overall survival in AML patients. In addition to AML, aberrant BCL2 overexpression is identified in patients with high‐risk myelodysplastic syndromes (MDS), and in vitro sensitivity to BCL2 inhibition in primary samples from patients with high‐risk MDS or secondary AML has been characterized. BCL2 overexpression has http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Hematology Wiley

Clinical experience with the BCL2‐inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies

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References (33)

Publisher
Wiley
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
0361-8609
eISSN
1096-8652
DOI
10.1002/ajh.25000
Publisher site
See Article on Publisher Site

Abstract

INTRODUCTIONWhile the past decade has improved our understanding of acute myeloid leukemia (AML) as a heterogeneous and clonal hematopoietic malignancy, the outcome of adult patients with AML and other myeloid malignancies remains poor. This is especially true in the relapsed and/or refractory (R/R) adult AML population, where available therapies are limited, responses are inadequate and long‐term survival and cure rates remain <10%. Proceeding to a successful curative stem cell transplant (SCT) in the relapsed setting is possible for only a minor proportion of R/R patients. Encouragingly, targeted therapeutic options for AML patients harboring certain mutations (i.e., IDH2, FLT3) or surface markers (i.e., CD33) now exist, improving upon the standard of care and generating hope for effective small molecule and targeted strategies for additional AML subsets.The antiapoptotic protein B‐cell leukemia/lymphoma‐2 (BCL2) is overexpressed in hematologic malignancies, where it has been implicated in the maintenance and survival of AML cells, therapeutic resistance, and associates with poor overall survival in AML patients. In addition to AML, aberrant BCL2 overexpression is identified in patients with high‐risk myelodysplastic syndromes (MDS), and in vitro sensitivity to BCL2 inhibition in primary samples from patients with high‐risk MDS or secondary AML has been characterized. BCL2 overexpression has

Journal

American Journal of HematologyWiley

Published: Jan 1, 2018

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