Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM.


Journal

European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985

Informations de publication

Date de publication:
May 2019
Historique:
received: 28 01 2019
revised: 29 01 2019
accepted: 30 01 2019
pubmed: 7 2 2019
medline: 15 11 2019
entrez: 7 2 2019
Statut: ppublish

Résumé

Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL-2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL-2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non-responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.

Identifiants

pubmed: 30725494
doi: 10.1111/ejh.13218
pmc: PMC6849823
doi:

Substances chimiques

Antineoplastic Agents 0
BCL2 protein, human 0
Bcl-2-Like Protein 11 0
Biomarkers, Tumor 0
Bridged Bicyclo Compounds, Heterocyclic 0
Proto-Oncogene Proteins c-bcl-2 0
Sulfonamides 0
venetoclax N54AIC43PW

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

437-441

Subventions

Organisme : Austrian Science Fund FWF
ID : I 3282
Pays : Austria

Informations de copyright

© 2019 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

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Auteurs

Florian Huemer (F)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Thomas Melchardt (T)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Bettina Jansko (B)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Adam Wahida (A)

Medizinische Klinik für Hämatologie und Internistische Onkologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Stefanie Jilg (S)

Medizinische Klinik für Hämatologie und Internistische Onkologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Philipp J Jost (PJ)

Medizinische Klinik für Hämatologie und Internistische Onkologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Eckhard Klieser (E)

Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria.

Katja Steiger (K)

Comparative Experimental Pathology and Digital Pathology, Institute of Pathology and Pathological Anatomy, Technical University of Munich, Munich, Germany.

Teresa Magnes (T)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Lisa Pleyer (L)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Sigrun Greil-Ressler (S)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Christof Rass (C)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Richard Greil (R)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

Alexander Egle (A)

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, Salzburg, Austria.

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