Dr. Shallis on the Investigation of Uproleselan in AML

Rory Shallis, MD, assistant professor of Medicine, Hematology, Yale School of Medicine, discusses the investigation of uproleselan (GMI-1271) in acute myeloid leukemia (AML).

Uproleselan is a small molecule, E-selectin inhibitor that has been shown to disrupt the microenvironmental protection of leukemia cells, according to Shallis. The agent mobilizes those cells into circulation and improves responses observed with traditional chemotherapy options, Shallis says. Notably, the efficacy of the agent does not appear to be dependent on a specific set of genetic or molecular profiles, Shallis adds. Rather, efficacy with uproleselan appears to be disease biology agnostic, according to Shallis.

This agent has been evaluated in combination with multiagent chemotherapy as part of a phase 1/2 trial (NCT02306291). The combination elicited a remission rate of 41% in the salvage cohort, with a complete response rate of 35%, Shallis adds. The data indirectly mirrored historical expectations of other treatments for patients in this setting, but there were no clear differences in time to or quality of count recovery, Shallis explains. 

The addition of uproleselan to chemotherapy resulted in low rates of toxicity, with lower-than-expected rates of mucositis were observed, Shallis notes; this is attributed to the role that E-selectin expression has on inflammation. According to Shallis, this may be relevant for older patients with AML who have other comorbidities that may make the risk of mucositis more problematic, Shallis concludes.