Findings from phase 3 uproleselan study in AML not all negative

Although uproleselan combined with chemotherapy did not outperform chemotherapy alone with respect to the primary efficacy endpoint in patients with relapsed or refractory acute myeloid leukaemia (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 tumour cells and the bone marrow microenvironment,” explained Dr Daniel DeAngelo (Dana-Farber Cancer Institute, MA, USA). 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 randomised 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 who were 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 2 treatment regimens were very comparable. “The observed adverse events 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 (subgroups of) the relapsed or refractory AML population. The drug is also being evaluated in patients with newly diagnosed AML (NCT03701308).

1. DeAngelo DJ, et al. Efficacy and safety of uproleselan combined with chemotherapy vs chemotherapy alone in relapsed/refractory acute myeloid leukemia: findings from an international phase 3 trial. Abstract 733, 66^th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.

Medical writing support was provided by Robert van den Heuvel.

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Posted on 11 December 202411 December 2024