@article{4737a0bfa6d44174be4bc02e044a8e94,
title = "Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias",
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.",
keywords = "Acute myeloid leukemia, BCR/ABL, Chronic myeloid leukemia, Decitabine, Myeloid blast phase, Philadelphia chromosome-positive acute myeloid leukemia, Ponatinib, Tyrosine kinase inhibitors, Venetoclax",
author = "Abhishek Maiti and Franquiz, {Miguel J.} and Farhad Ravandi and Cortes, {Jorge E.} and Jabbour, {Elias J.} and Koji Sasaki and Kayleigh Marx and Daver, {Naval G.} and Kadia, {Tapan M.} and Konopleva, {Marina Y.} and Lucia Masarova and Gautam Borthakur and DInardo, {Courtney D.} and Kiran Naqvi and Sherry Pierce and Kantarjian, {Hagop M.} and Short, {Nicholas J.}",
note = "Funding Information: This study was supported in part by the MD Anderson Cancer Center Support Grant CA016672 from the National Cancer Institute. N.J.S. is supported by the K12 Paul Calabresi Clinical Oncology Scholar Award and the American Society of Hematology Junior Faculty Scholar Award in Clinical Research. Funding Information: A.M.: research funding from Celgene Corporation; F.R.: research funding from Amgen, Bristol-Myers Squibb, Merck, Seattle Genetics, Sunesis Pharmaceuticals, and honoraria from Amgen, Pfizer, Seattle Genetics, Sunesis Pharmaceuticals; consulting or advisory role for Amgen, Seattle Genetics, Sunesis Pharmaceuticals; J.E.C.: research funding from Ambit BioSciences, ARIAD, Arog, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Celator, Cel-gene, Novartis, Pfizer, Sanofi, Sun Pharma, Teva; consultant for Ambit BioSciences, ARIAD, Astellas Pharma, BiolineRx, Bristol-Myers Squibb, Novartis; Pfizer; E.J.J.: consultancy/research funding from Takeda, BMS, Adaptive, Amgen, AbbVie, Pfizer, Cycla-cel; K.S.: Otsuka (honoraria) and Pfizer (consultancy); N.G.D.: consultancy from Sunesis Pharmaceuticals, Karyopharm, Pfizer, Bristol-Myers Squibb, Novartis Pharmaceuticals, Otsuka America Pharmaceutical, Jazz; research funding from Karyopharm, Immunogen, Pfizer, Incyte, Bristol-Myers Squibb, Daiichi-Sankyo, Ki-romic; and honoraria from Incyte; T.M.K.: none, M.Y.K.: Cali-thera (research funding); Stemline Therapeutics (consultancy, honoraria, and research funding); Forty-Seven (consultancy and honoraria); Eli Lilly (research funding); AbbVie (consultancy, honoraria, and research funding); Cellectis (research funding); Amgen (consultancy and honoraria); Hoffman La-Roche (consultancy, honoraria, and research funding); Genentech (honoraria and research funding); Ascentage (research funding); Kisoji (consultancy and honoraria); Reata Pharmaceuticals (equity ownership and patents & royalties); Ablynx (research funding); Astra Zeneca (research funding); and Agios (research funding); G.B.: research funding from AbbVie, Incyte, and Janssen; C.D.D.: honoraria and research funding from AbbVie, Agios, Novartis, Celgene, and Daiichi-Sankyo; M.F., L.M., K.N., S.P., and K.M.: no conflicts of interest; H.M.K.: research funding from Ariad, Astex, BMS, Cy-clacel, Daiichi-Sankyo, Jazz, Novartis, Pfizer (also honoraria), Im- munogen (also honoraria), and honoraria from Actinium and Takeda; N.J.S.: Takeda Oncology (consultancy and research funding); AstraZeneca (consultancy); and Amgen (honoraria). Publisher Copyright: {\textcopyright} 2020 S. Karger AG. All rights reserved.",
year = "2020",
month = dec,
doi = "10.1159/000506346",
language = "English (US)",
volume = "143",
pages = "567--573",
journal = "Acta Haematologica",
issn = "0001-5792",
publisher = "S. Karger AG",
number = "6",
}