Photo Credit: Nemes Laszlo

Although uproleselan combined with chemotherapy did not outperform chemotherapy alone concerning the primary efficacy endpoint in patients with relapsed or refractory acute myeloid leukemia (AML), the authors of the current phase 3 study observed some interesting trends in subgroup analyses.

“The E-selectin antagonist uproleselan is designed to disrupt the relationship between tumor cells and the bone marrow microenvironment,” explained Daniel DeAngelo, MD, PhD, from the Dana-Farber Cancer Institute, Massachusetts. Dr. DeAngelo’s research team evaluated the efficacy of this agent in a phase 3 study (NCT03616470)¹. The 380 enrolled patients with AML who were primary refractory or had a first or second relapse were randomly assigned 1:1 to chemotherapy plus uproleselan or to chemotherapy plus a placebo. Overall survival (OS) was the primary endpoint of the study.

The median OS was 13.0 months in the uproleselan arm and 12.3 months in the placebo arm, a non-significant difference (HR 0.89; 95% CI 0.69–1.15; P=0.39). In addition, the 24-month OS rate was 42% and 34%, respectively. “We did notice some interesting trends when looking at stratification factors and subgroups,” said Dr. DeAngelo. If patients were on a backbone of fludarabine, cytarabine, idarubicin (FLA-IDA), they appeared to benefit more from uproleselan (median OS 30 months; HR 0.73; 95% CI 0.50-1.06) than if they were on a backbone of mitoxantrone, etoposide, and cytarabine (MEC) (median OS 13 months; HR 1.06; 95% CI 0.75–1.51). Also, for patients who received a transplant in a subsequent phase, those treated with uproleselan had a better survival outcome than those who had not received uproleselan (HR 0.59; 95% CI 0.38–0.91). Dr. DeAngelo further noted that patients with primary refractory disease may benefit from additional uproleselan, whereas patients with relapsed disease are unlikely to benefit from this agent.

Finally, the safety profiles of the two treatment regimens were very comparable. “The observed AEs were consistent with the known side-effect profiles of the chemotherapy backbones that were administered,” according to Dr. DeAngelo.

Although uproleselan did not meet its primary endpoint in the current phase 3 study, the subgroup analyses provided encouraging data to further explore this agent in the relapsed or refractory AML population. The drug is also being evaluated in patients with newly diagnosed AML (NCT03701308).

Medical writing support was provided by Robert van den Heuvel.

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