@article{53520c38008242998fb41789e1fff91e,
title = "BL-8040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed/refractory acute myelogenous leukemia: An open-label safety and efficacy phase 2a study",
abstract = "Background: CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high-affinity CXCR4 antagonist BL-8040 with high-dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML. Methods: Forty-two patients received treatment with BL-8040 monotherapy for 2 days followed by a combination of BL-8040 with HiDAC for 5 days. Six escalating BL-8040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg/kg), and 1.5 mg/kg was selected as the dose for the expansion phase (n = 23). Results: BL-8040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL-8040 doses ≥1.0 mg/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5-mg/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5-mg/kg phase, and 21.8 months for responding patients in the 1.5-mg/kg cohort. Two days of BL-8040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold-changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts. Conclusions: The current results demonstrate the efficacy of CXCR4 targeting with BL-8040 and support continued clinical development in acute myelogenous leukemia.",
keywords = "BL-8040, CXCR4, acute myelogenous leukemia (AML), cytarabine",
author = "Gautam Borthakur and Yishai Ofran and Tallman, {Martin S.} and James Foran and Uy, {Geoffrey L.} and DiPersio, {John F.} and Showel, {Margaret M.} and Avichai Shimoni and Arnon Nagler and Rowe, {Jacob M.} and Altman, {Jessica K.} and Michal Abraham and Amnon Peled and Stephen Shaw and Osnat Bohana-Kashtan and Ella Sorani and Yaron Pereg and Adam Foley-Comer and Galia Oberkovitz and Lustig, {Tzipi M.} and Irit Glicko-Kabir and Arnon Aharon and Abi Vainstein-Haras and Kadosh, {Shaul E.} and Emil Samara and Al-Rawi, {Ahmed N.} and Naveen Pemmaraju and Carlos Bueso-Ramos and Cortes, {Jorge E.} and Michael Andreeff",
note = "Publisher Copyright: {\textcopyright} 2020 American Cancer Society",
year = "2021",
month = apr,
day = "15",
doi = "10.1002/cncr.33338",
language = "אנגלית",
volume = "127",
pages = "1246--1259",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "8",
}
