CX-01, a Low Anticoagulant Heparin, May Enhance Count Recovery and Treatment Efficacy in Acute Myeloid Leukemia

• Published in: Blood 2016-12, Vol.128 (22), p.5220-5220
• Main Authors: Kovacsovics, Tibor J., Mims, Alice S., Salama, Mohamed E, Pantin, Jeremy M, Kosak, Ken M, Rao, Narayanam, Ahorukomeye, Peter, Glenn, Martha, Deininger, Michael W., Boucher, Kenneth M, Bavisotto, Linda M, Gutierrez-Sanchez, Gerardo, Kennedy, Thomas P, Marcus, Stephen Garrett, Shami, Paul J
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.5220.5220

Acute myeloid leukemia (AML) therapy is associated with pancytopenia and with a high failure rate due to resistant leukemia stem cells that home to marrow niches. We present here updated results of this study that combined the low anticoagulant heparin CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7+3) along with CX-01. Patients younger than 60 received consolidation therapy with high dose cytarabine along with CX-01. Twelve patients were enrolled (median age 56; range 22 - 74; 3 women). Three, 5, and 4 patients had good, intermediate, and poor risk disease, respectively. Two patients did not finish induction due to events unrelated to CX-01. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had a morphologic complete remission after one induction (CR1), including all patients with de novo AML (11/11). No patient required re-induction at Day 14. Eight patients are alive at a median follow-up of 24 months (range 13 - 29). Four patients remain in CR1. Four patients received an allogeneic stem cell transplant in CR1. All patients who received a full induction were evaluable for platelet recovery and had a median day to an untransfused platelet count ≥ 20,000/μl of 21. Five patients who received a full induction without myelopoietic growth factor support were evaluable for neutrophil recovery and had a median time to a neutrophil count ≥ 500/mL of 22 days (mean 22.6 ± 2.4, range 21 - 27). Median disease free survival was 14.8 months. Median overall survival was not attained at the maximum follow up time of 29.4 months. No CX-01-associated serious adverse events occurred. In a supplemental surface plasmon resonance study, CX-01 inhibited binding of CXCL12 to surface conjugated heparin with a 50% inhibitory concentration (IC50) of 4.7 nM, suggesting the possibility that CX-01 may enhance CR by disrupting the CXCL12-mediated leukemic stem cell marrow niche. We conclude that CX-01 is well tolerated when combined with intensive therapy for AML. It appears to be associated with enhanced count recovery and treatment efficacy. Thus, CX-01 warrants further study in this setting. Kovacsovics:Seattle Genetics: Research Funding. Deininger:CTI BioPharma Corp.: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Res