2102-HEM-101 phase II: Final 5-year results of olutasidenib in R/R mIDH1 AML

Results from the phase II, open-label, multicenter 2102-HEM-101 trial (NCT02719574) of olutasidenib in 153 adult patients with relapsed/refractory (R/R) mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid leukemia (AML) were recently published by Cortes et al. in the Journal of Hematology & Oncology. The primary efficacy endpoint was rate of complete remission (CR) including CR with partial hematologic recovery (CRh).

Key data: In the efficacy-evaluable population (n = 147), olutasidenib achieved a CR/CRh rate of 35% (p < 0.001; 95% confidence interval [CI], 27–43). The median duration of CR/CRh was 25.3 months (95% CI, 13.5–not reached), and the median overall survival (OS) was 11.5 months (95% CI, 8.3–15.5). The overall response rate (ORR) was 48% (n = 71; 95% CI, 40–56.7). Response rates were higher in patients with 1–2 prior regimens (CR/CRh, 41%; ORR, 54%) compared with those receiving ≥3 prior regimens (CR/CRh, 24%; ORR, 39%). No new safety signals were identified, and no new patients discontinued treatment beyond Year 3. 

Key learning: The long-term data demonstrate durable efficacy and a manageable safety profile of olutasidenib in patients with R/R mIDH1 AML, including heavily pretreated patients. Findings support treatment continuation for at least 6 months to achieve clinical response. Higher response rates with earlier lines of therapy suggest the potential benefit of initiating olutasidenib earlier in the R/R setting.