PS1042 ISOCITRATE DEHYDROGENASE 1/2 MUTATIONS AND ASSOCIATIONS IN ACUTE MYELOID LEUKEMIA
Authors: P. Kovy, A. Kozma, E. Adam, A. Borsy, A. Bors, N. Meggyesi, J. Dolgos, N. Lovas, G. Mikala, P. Remenyi, H. Andrikovics
Journal: HemaSphere (2019)

Background: Isocitrate dehydrogenase 2 (IDH2) mutations are linked to DNA hypermethylation, altered gene expression, and blocked differentiation of hematopoietic progenitor cells, which may trigger myeloid malignancies. Between 9% and 15% of newly diagnosed acute myeloid leukemia (AML) cases are associated with IDH2 mutations. Mutant IDH2 (mIDH2) inhibitors have recently entered clinical development and may be a promising treatment strategy for patients with mIDH2 AML. However, treatment patterns and outcomes in patients with relapsed or refractory (R/R) mIDH2 AML are ill-defined, which precludes an accurate assessment of the clinical benefit provided by mIDH2 inhibitors. Aims: The primary objective of this study was to describe treatment patterns and associated outcomes in patients with mIDH2 R/R AML. Methods: This was a retrospective, multicenter, medical chart review study, collecting data from 104 patients with mIDH2 R/R AML in France. Patients aged ≥18 years were eligible if they had been hospitalized for mIDH2 R/R AML between September 2011 and September 2016. Patients treated with the mIDH2 inhibitor enasidenib were excluded. Demographic data, disease characteristics, treatments received after diagnosis of R/R AML, response assessments, and date of death were extracted from medical charts. Overall survival (OS) was estimated by means of Kaplan–Meier curves. Results: Overall, 104 patients were selected from 9 French sites and 103 patients were included in the analysis. 70% of patients had received 1 line of therapy prior to baseline while 30% of patients had >1 line of therapy before baseline. Median age was 65 years and 57% of patients were male. A total of 23 patients received best supportive care (BSC) after baseline. For the remaining 80 patients who received ≥1 line of therapy after baseline, the most common regimen types were low-intensity chemotherapy, used in 38 patients (mainly 5-azacytidine), followed by intensive chemotherapy regimens, used in 26 patients (mainly 7+3 and cytarabine-containing regimens). Best post-baseline response was assessed in 94 patients. Among these patients, 28 (30%) were responders: 21 patients had a complete response (CR), 5 had a partial response, 1 patient had a CR with incomplete hematologic recovery, and 1 patient had CR with incomplete platelet recovery. The remaining 66 patients (70%) were non-responders; among these patients, 9 had stable disease and 27 had progressive disease. At the cutoff date for this study (November 13, 2018), 72% of patients had died, while 28% of patients were censored as still alive at the time of last information. Median OS from baseline was 7.20 months (95% confidence interval [CI] 4.30–10.71) (Figure).Summary/Conclusion: Patients with mIDH2 R/R AML receiving standard of care had a median OS of 7.20 months. While this result cannot be directly compared with the single-arm study of enasidenib, the only currently approved IDH2 inhibitor for use in R/R AML, (median OS 8.8 months) due to potential differences in patient population, it provides a much-needed description of actual treatment patterns and associated outcomes in patients with mIDH2 R/R AML.