Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias

Abhishek Maiti, Miguel J. Franquiz, Farhad Ravandi, Jorge E. Cortes, Elias J. Jabbour, Koji Sasaki, Kayleigh Marx, Naval G. Daver, Tapan M. Kadia, Marina Y. Konopleva, Lucia Masarova, Gautam Borthakur, Courtney D. Dinardo, Kiran Naqvi, Sherry Pierce, Hagop M. Kantarjian, Nicholas J. Short

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Philadelphia chromosome-positive (Ph+) advanced leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) in myeloid blast phase (MBP), have poor outcomes. Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKI) in preclinical studies. However, clinical activity of venetoclax and TKI-based regimens is unknown. Methods: We conducted a retrospective study on patients with Ph+ AML (n = 7) and CML-MBP (n = 9) who received venetoclax combined with TKI-based regimens at our institution. Results: Median patient age was 42 years, and the median number of prior therapy cycles was 5 (range 2-8). Nine patients received decitabine-based, and 7 received intensive chemotherapy-based regimens. Ten patients (63%) received ponatinib. The overall response rate (ORR) in 15 evaluable patients was 60% (1 complete remission [CR], 6 CR with incomplete hematologic recovery [CRi], 1 morphologic leukemia-free state, and 1 partial response). The ORR was 43% in Ph+ AML and 75% in CML-MBP. The median overall survival (OS) for all patients was 3.6 months, for AML OS was 2.0 months, and for CML-MBP OS was 10.9 months. The median relapse-free survival for AML and CML-MBP was 3.6 and 3.9 months, respectively. Compared to nonresponders, patients achieving CR/CRi had higher baseline Ph+ metaphases and BCR-ABL1 PCR. Conclusions: Combination therapy of venetoclax with TKI-based regimens shows encouraging activity in very heavily pretreated, advanced Ph+ leukemias, particularly CML-MBP. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Original languageEnglish (US)
JournalActa Haematologica
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • BCR/ABL
  • Chronic myeloid leukemia
  • Decitabine
  • Myeloid blast phase
  • Philadelphia chromosome-positive acute myeloid leukemia
  • Ponatinib
  • Tyrosine kinase inhibitors
  • Venetoclax

ASJC Scopus subject areas

  • Hematology

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