Citations 1
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
Ofran, Yishai , Tallman, Martin S. , Foran, James M. , Uy, Geoffrey L. , Showel, Margaret M. , Shimoni, Avichai , Nagler, Arnon , Rowe, Jacob M. , Altman, Jessica K. , Abraham, Michal , Peled, Amnon , Shaw, Stephen M., Bohana‐Kashtan, Osnat, Sorani, Ella, Pereg, Yaron , Foley‐Comer, Adam, Oberkovitz, Galia, Lustig, Tzipi, Glicko‐Kabir, Irit, Aharon, Arnon, Vainstein‐Haras, Abi, Kadosh, Shaul, Samara, Emil, Al-Rawi, Ahmed , Pemmaraju, Naveen , Bueso‐Ramos, Carlos E. , Cortes, Jörge E. , Foran, James M , Shimoni, Avichai , Cortes, Jorge , Uy, Geoffrey , Borthakur, Gautam , DiPersio, John F. , Andreeff, Michael
Cancer | December 3, 2020 | Volume: 127 | Issue: 8 | Pages: 1246-1259
BackgroundCXCR4 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.MethodsForty‐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).ResultsBL‐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.ConclusionsThe current results demonstrate the efficacy of CXCR4 targeting with BL‐8040 and support continued clinical development in acute myelogenous leukemia.