Indoleamine 2,3-dioxygenase (IDO) is a marker for poor prognosis in patients with acute myeloid leukemia (AML). Indoximod is an oral small-molecule inhibitor of IDO that acts directly on immune cells to reverse IDO pathway-mediated suppression. At the 60th American Society of Hematology Annual Meeting & Exposition, Ashkan Emadi from the University of Maryland School of Medicine, Baltimore, US, presented data from an open-label, multicenter phase I study (NCT02835729), whose primary objectives were to assess the safety and preliminary efficacy of indoximod in combination with standard chemotherapy in adult patients with newly diagnosed AML.
Thirty-three patients (median age = 54 years; range, 18–72) with newly diagnosed AML were treated with indoximod in combination with induction chemotherapy (cytarabine 100 mg/m2/d for 7 days and idarubicin 12 mg/m2/d for 3 days). Using a “3+3” design, indoximod (600 mg [dose level 0], 1000 mg [dose level 1], 1200 mg [dose level 2]) was given orally every 8 hours (Q8h) starting on day 9 of induction.
- No dose-limiting toxicities were observed
- Recommended phase 2 dose: 1200 mg Q8h
- Grade ≥ 3 hematologic adverse events (AEs) occurring in ≥ 9% of patients include febrile neutropenia (82%), anemia (12%) and thrombocytopenia (9%)
- Three patients experienced fatal AEs which were deemed unrelated to indoximod
- Clinical activity in evaluable patients (n = 22)
- Complete remission (CR) plus CR with incomplete count recovery (CRi): 73% (16/22)
- Measurable residual disease (MRD) assessment (< 0.02% by flow) was available for 14 patients post-induction
- MRD negativity was observed in 86% (12/14) of patients
- MRD positivity was observed in 14% of patients (2/14)
- Of the 14 patients tested for MRD, 13 started HiDAC consolidation
- All 13 patients were MRD negative post-HiDAC-1 consolidation
- There was no statistical correlation between IDO expression and clinical outcome
In summary, indoximod in combination with standard chemotherapy was well tolerated and the overall adverse event profile was consistent with the profile of induction and consolidation therapy in AML. In addition, evidence of clinical activity was observed by a post-induction MRD negativity rate of 86% and a post-HiDAC-1 MRD negativity of 100%.