IDO-1 inhibitor therapies, which are currently in clinical trials, may benefit some patients with acute myeloid leukemia (AML). Researchers report in the Nature journal Scientific Reports that IDO (indoleamine 2, 3 dioxygenase) expression may be an important indicator of outcomes in patients with AML. The investigators have discovered that IDO expression is highest in patients who have poor survival and this enzyme may be an independent indicator after adjusting for other known variables.
The researchers found that high levels of IDO at diagnosis also identify those who might benefit most by taking an IDO inhibitor along with their standard therapy. “Some patients tend to respond better to chemotherapy and some patients tend to relapse and so that is what we wanted to look at,” said study investigator Ravindra Kolhe, MD, a breast and molecular pathologist and director of the Georgia Esoteric & Molecular Labs LLC in the Department of Pathology at the Medical College of Georgia at Augusta University, Augusta, Georgia.
Dr. Kohle and his colleagues conducted a review of 40 cases of AML and found increased IDO expression in the bone marrow biopsy (performed to diagnose their disease) correlated with lower overall survival rates and early mortality. He said the findings suggest that IDO expression should routinely be measured when the diagnostic bone marrow biopsy is performed.
The investigators conducted a univariate analysis and found that higher age, male gender, high-risk cytogenetics, higher IDO-1 mRNA, higher composite IDO-1 score, and not undergoing allogeneic stem cell transplant (ASCT) predicted poor overall survival. They also conducted a multivariate analysis and found that higher composite IDO-1 score and not undergoing ASCT predicted poor outcomes. In addition, patients who failed induction therapy had higher composite IDO-1 scores.
An early-phase clinical study is already underway exploring the clinical potential of an IDO inhibitor in this patient population (Clinical Trials Identifier: NCT02835729). “This is a significant advance. One of the problems with AML is that patients who relapse have a 70% chance of dying early, so the first relapse is considered a failure for treatment,” Dr. Kolhe said in an interview with OncoTherapy Network.
In leukemia, stem cells get stuck in a blast state so they don't mature; however, the researchers discovered that the one thing the blasts are producing is IDO. Dr. Kolhe said the patients in this study who died at 6 months had a high expression of IDO, while the blasts produced relatively little IDO in the patients who lived 5 years or longer. He and his colleagues concluded that a composite IDO-1 score may be a prognostic tool that can help identify a certain subset of AML patients with the highest risk for early mortality.