ASH 2018 | Enasidenib for the treatment of previously untreated IDH2-mutated acute myeloid leukemia - results from the Beat AML Master Trial

The Beat AML Master trial is a precision medicine trial which enrolled newly diagnosed patients who are 60 years of age or older. Patients are assigned to an interventional sub-study based upon an algorithm integrating cytogenetic and mutational analysis, all within 7 days of enrollment. At the 60^th American Society of Hematology Annual Meeting & Exposition, Eytan Stein from the Memorial Sloan Kettering Cancer Center, New York, US, presented data from a sub-study of the Beat AML master trial.

Eytan Stein presented results from a phase Ib/II study which is evaluating the efficacy of the enasidenib, an oral inhibitor of isocitrate dehydrogenase 2 (IDH2), in patients who are 60 years or older with newly diagnosed IDH2-mutant acute myeloid leukemia (AML). The primary objective of this phase Ib/II study was overall response rate. The key secondary objectives were progression-free survival (PFS), overall survival (OS) and to explore the toxicity profile of combining enasidenib with azacitidine.

Twenty-eight patients (median age = 75.0 years; range, 62–84) with previously untreated IDH2-mutated AML were enrolled in this study. Of these, 27 patients received enasidenib 100 mg/day in continuous 28-day cycles. Azacitidine (75 mg/m² days 1–7) was added to enasidenib for patients not achieving a complete remission (CR) or complete remission with incomplete hematologic recovery (CR/CRi) by cycle 5.

Key findings:

• The most common non-hematologic adverse events (AEs) occurring in ≥ 10% of patients were differentiation syndrome (21.4%), hypophosphatemia (21.4%), hypertension (17.9%), hyponatremia (14.3%) and sepsis (14.3%)
• The most common severe AEs occurring in ≥ 5% of patients were differentiation syndrome (21.4%), sepsis (14.3%), pneumonia (7.1%), cellulitis (7.1%), increased bilirubin (7%) and pyrexia (7.1%)
• Overall response rate: 44.4% (12/27)
  • CR rate: 37% (10/27)
  • CRi rate: 7.4% (2/27)
• No response was seen in 15 patients, with nine moved to combination therapy with azacitidine
• Early death within 30 days: 0%

In summary, enasidenib monotherapy is safe and effective in patients aged 60 years or older with previously untreated IDH2-mutated AML.

In an interview with the AML Global Portal (AGP), Eytan Stein noted that the results of this study were “remarkable” and may represent a “real leap” in the treatment of IDH2-mutated AML. He highlighted that differentiation syndrome, an important severe AE, should be monitored in patients frequently and treated with steroids.