Impact of Induction Chemotherapy on RAS Mutations in AML
Posted: Tuesday, May 4, 2021
Patients with acute myeloid leukemia (AML) who undergo induction therapy tend to have high RAS pathway mutation clearance rates, suggesting that RAS mutations may not be a driver of relapse. Eytan M. Stein, MD, of the Memorial Sloan Kettering Cancer Center, New York, and colleagues published these findings in a letter to the editor in the American Journal of Hematology.
The study authors retrospectively analyzed data from 232 patients with AML who had next-generation sequencing before treatment. All patients had undergone intensive induction chemotherapy between April 2014 and May 2019. Chemotherapy regimens included intravenous cytarabine paired with an anthracycline. A total of 40 patients received targeted therapy in addition to induction chemotherapy. There were 196 patients with wild-type RAS genes, and 20 patients had mutations in NRAS, 11 (5%) had mutations in KRAS, and 5 patients (2%) had mutations in both NRAS and KRAS.
After a median follow up of 21.3 months after induction, the median event-free survival was 2.9 months among KRAS-mutated patients, 8.6 months among NRAS-mutated patients, and 13.8 months in patients with wild-type disease. The median overall survival was 5.2 months, 35.2 months, and 30.1 months in patients with mutations in KRAS, NRAS, or wild-type, respectively. In addition, the 12-month cumulative incidence of relapse was significantly increased in patients with four or more co-mutations (50%) compared with patients who had fewer than four co-mutations (20.4%).
Within this population, 42 patients experienced relapse, and 35 patients had sequencing obtained at the time of relapse. There were eight NRAS mutations and one KRAS mutation present at the time of diagnosis in the relapse cohort; however, just two NRAS mutations were still present after chemotherapy at the time of relapse. Other mutations in the RAS pathway, including the PTPN11 and CBL genes, were also cleared after induction chemotherapy. However, 30 new mutations were detected among the 35 patients at the time of relapse.
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