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

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)567-573
Number of pages7
JournalActa Haematologica
Volume143
Issue number6
DOIs
StatePublished - Dec 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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