Dr Daver on the Potential Utility of Uproleselan in R/R AML

Naval G. Daver, MD, professor, director, Leukemia Research Alliance Program, Department of Leukemia, Division of Cancer Medicine, The University of MD Anderson Cancer Center, discusses the potential utility of uproleselan in patients with relapsed/refractory acute myeloid leukemia (AML).

The E-selectin inhibitor uproleselan is among the most advanced therapies currently in clinical development for AML, Daver begins. Uproleselan has been evaluated in a randomized phase 3 study (NCT03616470) in combination with intensive chemotherapy in patients with relapsed/refractory AML, he states. The study compared the combination of uproleselan with either FAI (fludarabine, cytarabine, and idarubicin) or MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy regimens against chemotherapy alone, with the primary end point being overall survival, Daver explains. The final results of this event-based study are anticipated later in 2024, depending on when the required number of events occur, he reports.

If the study’s outcome is positive, it may lead to the approval of uproleselan in combination with intensive chemotherapy as an effective salvage treatment for relapsed AML, Daver continues. Moreover, there is potential for uproleselan to be incorporated into various frontline treatment regimens, such as those involving hypomethylating agents, venetoclax (Venclexta), and other intensive chemotherapies like gemtuzumab ozogamicin (Mylotarg), he says.

One of the key advantages of targeting the E-selectin pathway is that it is ubiquitously expressed in AML, meaning it does not require a specific biomarker or molecular cytogenetic aberration for its effectiveness, Daver continues. This broad applicability makes uproleselan an attractive candidate for use in combination therapies across different AML subtypes, according to Daver. Additionally, early findings indicate that uproleselan is associated with reduced rates of mucositis and other toxicities, further enhancing its appeal as an adjunct to existing standard-of-care treatments, he says.

Although the early results are promising, confirmation of uproleselan’s efficacy and safety will depend on the forthcoming phase 3 data, Daver emphasizes. Should these results be favorable, uproleselan could become a commercially available, new, and potentially safer treatment approach for patients with AML, he concludes.