Results from a phase Ib/II study presented at the 23rd Congress of the European Hematology Association suggest that combining an IDH inhibitor (ivosidenib or enasidenib) with the hypomethylating agent azacitidine leads to high response rates in older patients with previously untreated acute myeloid leukemia (AML). According to lead author and presenter Courtney D. DiNardo, MD, from the University of Texas MD Anderson Cancer Center in Houston, “the combination of azacitidine with an oral IDH inhibitor was well tolerated, and randomized studies are ongoing,” she told ASH Clinical News. The early-phase trial enrolled adults with mutant IDH-positive, newly diagnosed AML who had an Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤2 and were considered ineligible for intensive chemotherapy. Dr. DiNardo presented data from the dose-finding and dose-expansion phases of the trial, during which 29 participants received treatment in continuous 28-day cycles. All patients received azacitidine 75 mg/m2 for a total of seven days plus an IDH inhibitor at one of the following dose levels:
- once-daily ivosidenib 500 mg (n=23)
- once-daily enasidenib 100 mg (n=3)
- once-daily enasidenib 200 mg (n=3)
- complete remission (CR): 10 patients (44%) in the ivosidenib arm and 3 patients (50%) in the enasidenib arm
- CR with incomplete count recovery: 5 (22%) and 0
Reference DiNardo CD, Stein AS, Stein EM, et al. Mutant IDH (MIDH) inhibitors, ivosidenib or enasidenib, with azacitidine (AZA) in patients with acute myeloid leukemia (AML). Abstract #S1562. Presented at the EHA 23rd Congress, June 17, 2018; Stockholm, Sweden.