Dr Watts on the Final Results of the 2102-HEM-101 Trial in IDH1-Mutated AML

Justin M. Watts, MD, associate professor, medicine, Division of Hematology, chief, Leukemia Section, University of Miami Sylvester Comprehensive Cancer Center, discusses the final 5-year results from the phase 2 2102-HEM-101 trial (NCT02719574) in the cohort of patients with IDH1-mutated acute myeloid leukemia (AML) who were treated with olutasidenib (Rezlidhia).

This pivotal phase 2 trial enrolled 153 patients with relapsed or refractory IDH-mutant AML who had progressed after standard therapies, often following multiple lines of treatment, Watts begins. The median number of prior therapies in this population was 2, including chemotherapy, hypomethylating agents, venetoclax (Venclexta), or previous transplants, Watts says. These patients received single-agent olutasidenib, administered as a single 150-mg pill twice daily, he reports. The treatment was notably well tolerated, and previously reported data showed a complete remission (CR)/CR with partial hematologic recovery (CRh) rate of 35% and an overall response rate (ORR) of 48% among efficacy-evaluable patients (n = 147), Watts explains.

A notable finding was the duration of response (DOR) among responders, especially those who achieved CR/CRh, he continues. For these patients, the median DOR was 25.3 months (range, 1.8-54.6), which is exceptional for relapsed/refractory AML treated with a single-agent targeted therapy, according to Watts. The 5-year follow-up data reaffirmed these findings, Watts states. The median overall survival (OS) for all patients was 11.6 months (range, 0.2-57.1), but this number was skewed by the poor outcomes in the non-responders (n = 78), who had a median OS of just 3.9 months (range, 0.2-32.6), Watts says. However, patients who respondedhad a median OS of approximately 3 years, he adds. For those who achieved CR/CRh, the median OS was not reached (range, 6.3-57.1+ months), with the OS curve indicating that more than 50% of these patients were still alive at the 5-year mark, Watts explains.

These results provide substantial confidence in using olutasidenib for patients with AML with IDH1 mutations, Watts emphasizes. If a patient responds to this treatment, there is a strong likelihood of a prolonged remission and significantly extended survival, Watts concludes.