By Leah Sherwood - Last Updated: August 10, 2022
A chemotherapy-free treatment with sorafenib and plerixafor plus granulocyte colony stimulating factor (G-CSF) mobilized leukemia cells to peripheral circulation and led to “encouraging rates of response” in patients with relapsed/refractory FLT3/ITD-mutated acute myelogenous leukemia (AML), according to a phase I study.
The study enrolled 28 patients with relapsed/refractory FLT3/ITD-mutated AML between December 2010 and December 2013. Patients received the FLT3/ITD inhibitor sorafenib, the SDF-1/CXCR4 inhibitor plerixafor, and G-CSF.
The response rate was 36%, with complete response reported in four patients, complete remission with incomplete platelet recovery reported in four patients, complete remission with incomplete hematologic recovery reported in one patient, and a partial response reported in one patient. The median response duration was 5.3 months.
No dose-limiting toxicities (DLTs) were encountered in the four-week DLT window of the study. However, hand-foot syndrome and rash were reported in some patients after the DLT window, and dose reductions were required in most patients, according to investigators.
A several-fold change in mobilization from bone marrow to peripheral blood circulation in the first two weeks of treatment was reported in CD34+ cells (mean, 98.6), CD34+/38− cells (mean, 47), CD34+/38−/CD123+ cells (mean, 77.5), CD44+ cells (mean, 37), VLA4+ cells (mean, 31.2), CXCR4+ cells (mean, 70.6), and absolute blast count (mean, 58.4).
The expression of CXCR4, CD44, and VLA4 on circulating leukemia cells was significantly negatively associated with the mobilization of CD34+/38−, CD34+/38−/123+ progenitor cells (P≤.002 for all).
The treatment strategy has “promising activity,” and the data “provide a rationale for combined inhibition of FLT3/ITD and stroma-mediated signaling that can potentially be added to chemotherapeutic or epigenetic agents in the frontline setting,” the authors concluded.
Borthakur G, Zeng Z, Cortes JE, et al. Phase 1 study of combinatorial sorafenib, G-CSF, and plerixafor treatment in relapsed/refractory, FLT3-ITD-mutated acute myelogenous leukemia patients. Am J Hematol. 2020;95(11):1296-1303.
Original Source: Sorafenib and Plerixafor Plus G-CSF Mobilizes Leukemia Cells, Leads to ‘Encouraging Rates of Response’ in FLT3/ITD-Mutated AML | Blood Cancers Today