Outcomes Associated with Conventional Salvage Therapy in Patients with Refractory or Relapsed AML and IDH1/IDH2 Mutations

Conference Correspondent - EHA 2016

A total of 2827 adults with acute myeloid leukemia (AML) (median age, 55 years; range, 18-84 years) who entered 8 prospective first-line AMLSG trials of intensive conventional induction and consolidation therapy were included in this retrospective study. Mutational status of IDH1 and IDH2 was assessed at the time of initial diagnosis using a combination of denaturing high-performance liquid chromatography followed by direct DNA sequencing.1 Overall, IDH1/2 mutations were identified in 530 (19%) patients: IDH1 mutations in 8% andIDH2 mutations in 11%. Eight patients had a mutation in both genes. All but one IDH1mutation involved codon R132. Among these 530 patients with IDH1/2-mutated AML, 62% achieved complete remission (CR) after initial induction therapy (IDH1, 64%; IDH2, 61%). A total of 138 patients had refractory disease (RD), including 83 patients who received 2 induction cycles. Two hundred eight IDH1/2-mutated patients relapsed (RE). Median overall survival (OS) in patients with RD (measured from date of RD) and in patients who relapsed (measured from date of RE) was 1.0 years and 0.8 years, respectively. Patients with IDH2 mutations had a longer OS (P = 0.003), a finding that is mainly attributed to cases carrying IDH2R172 mutations. Of the 82 patients with RD after 2 cycles of induction chemotherapy, 48% received allogeneic hematopoietic-cell transplantation (alloHCT). Their median OS was 1.8 years compared with 0.5 years in those who did not undergo alloHCT. Of the 208 RE patients, 153 received intensive chemotherapy or alloHCT, and 58% subsequently achieved a CR/CR with incomplete hematologic recovery. Seventy-four relapsed patients received alloHCT. Median OS after relapse of patients receiving alloHCT was 1.5 years compared with 0.6 years in those who did not undergo alloHCT. In summary, median OS results were 7.4 months for IDH1-mutated patients, 11.7 months forIDH2R140-mutated patients, and 21.2 months for IDH2R172-mutated patients. These outcomes after conventional salvage therapy in refractory and relapsed AML represent benchmarks for clinical trials evaluating IDH inhibitors in this clinical setting.
  1. Paschka P, et al. EHA 2016. Abstract S809.