According to research published in Blood, the addition of the novel E-selectin antagonist uproleselan to chemotherapy appears to be well tolerated and yielded high remission rates in patients with acute myeloid leukemia (AML).
The researchers conducted a multicenter, open-label, phase 1/2 study to evaluate the safety, tolerability, and antileukemic activity of uproleselan in patients with R/R AML and patients aged ≥60 years with newly diagnosed AML (ClinicalTrials.gov Identifier: NCT02306291).
In the dose-escalation phase of the study, patients with R/R AML received uproleselan, ranging from 5 to 20 mg/kg, in combination with the salvage chemotherapy regimen mitoxantrone, etoposide, and cytarabine (MEC). In the expansion phase, patients from the same R/R AML cohort received uproleselan at the recommended phase 2 dose (RP2D) in combination with MEC, and in a separate cohort, patient with newly diagnosed AML received uproleselan in combination with a standard (7 + 3) frontline AML induction regimen.
The primary endpoint was the frequency, severity, and relatedness of treatment-emergent adverse events (TEAEs) in patients receiving uproleselan in combination with chemotherapy. Clinical response (per the 2003 revised recommendations of the International Working Group for AML) and efficacy assessments were also conducted.
A total of 91 patients were enrolled in the study. The dose-escalation phase included 19 patients with R/R AML, and the expansion phase included 54 patients with R/R AML, including 7 from the dose-escalation phase, and 25 patients with newly diagnosed AML. The median age of was 59.0 years (range, 26-84) among all patients (n=66) with R/R AML and 67.0 (range, 60-79) among patients with newly diagnosed AML.
In the dose-escalation phase, no dose-limiting toxicities were observed among the 19 patients with R/R AML. The RP2D was established as 10 mg/kg twice daily.
In the expansion phase, patients with R/R AML who were treated with uproleselan (RP2D) plus MEC demonstrated a remission rate (complete response [CR]/CR with incomplete count recovery [CRi]) of 41%, with 35% of patients achieving CR. The median overall survival (OS) was 8.8 months. Of those achieving CR/CRi, 50% proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Patients with newly diagnosed AML who were treated with frontline uproleselan (RP2D) plus cytarabine and idarubicin (7 + 3) demonstrated a remission rate of 72%, with 52% of patients achieving CR. The median OS was 12.6 months. Of those achieving CR/CRi, 61% proceeded to receive allo-HSCT.
No patients with R/R AML discontinued treatment due to AEs. All patients in this group had evidence of grade 4 myelosuppression during the study. Most of the TRAEs were attributed to the background chemotherapy. The most common grade 3 or 4 TEAEs attributed to uproleselan were febrile neutropenia (17%), thrombocytopenia (11%), and anemia (8%). The rate of grade 3 mucositis occurring with uproleselan plus MEC was only 2%.
Among patients with newly diagnosed AML, nearly all reported toxicities were attributed to the effects of underlying leukemia and chemotherapy. The most common grade 3 or 4 TEAEs attributed to uproleselan were febrile neutropenia (12%), decreased white blood cell count (12%), anemia (8%), and pneumonia (8%).
Disclosure: This research was supported by GlycoMimetics. Please see the original reference for a full list of disclosures.
DeAngelo DJ, Jonas BA, Liesveld JL, et al. Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022;139(8):1135-1146. doi:10.1182/blood.2021010721