Association of acute myeloid leukemia (AML) patient, disease, and molecular characteristics with a long-term (LT) response to olutasidenib.

6523 Background: Mutations in isocitrate dehydrogenase 1 (m IDH1 ) occur in 7%-14% of patients with AML. Olutasidenib is a potent, oral small-molecule mIDH1 inhibitor that selectively inhibits IDH1 variants but preserves wild-type IDH1 function. The registrational phase 2 trial (NCT02719574) of olutasidenib in patients with relapsed/refractory (R/R) m IDH1 AML reported a complete remission (CR)/CR with partial hematologic recovery (CRh) rate of 35% and a median CR/CRh duration of 25.3 mo. This analysis examines patient, disease, and molecular characteristics of patients with a LT CR/CRh response to olutasidenib without transplant. Methods: Adults with R/R m IDH1 AML treated with olutasidenib 150 mg twice daily who had a CR/CRh and a duration of response (DOR) >12 mo were included. Overall survival (OS), DOR, event-free survival (EFS), and adverse events (AEs) were assessed. Univariate and multivariate logistic regression analyses were used to examine baseline factors that predicted DOR >12 vs ≤12 mo. Results: Of 147 evaluable patients, 51 (35%) achieved a CR/CRh; of these, 32 (63%) maintained a CR/CRh >12 mo. Excluding 6 patients who proceeded to transplant, 26 (51%) had a DOR >12 mo (Table). Among these patients at baseline, median age was 72 y; 69% were female; 73% had an R132C mutation; 12% had prior venetoclax; 88% were platelet transfusion independent (TI); 73% were red blood cell (RBC) TI. Patients had a median (range) of 2 (0, 5) comutations, most commonly DNMT3A (n=6) or NPM1 (n=5); 2 patients with NPM1 also had FLT3 mutations. Median (95% CI) time to response was 1.9 (1.0, 1.9) mo. Median OS and EFS were not reached. Estimated 48-mo OS was 74% (95% CI: 51%, 88%). Estimated 48-mo EFS was 69% (95% CI: 47%, 83%). 5 (19%) patients relapsed (including 1 after 24 mo); 10 (38%) patients were on treatment at data lock. Significant predictors of response >12 vs ≤12 mo by multivariate analysis were relapsed AML vs refractory AML (odds ratio [OR]: 0.19) and female sex (OR: 0.21). Age, number of comutations, m IDH1 variant, RTK pathway mutations, number of prior therapies, and baseline TI were not significant predictors. Common AEs were nausea (35%), increased ALT, asthenia, constipation, and cough (31% each). Common grade ≥3 AEs were increased ALT, gamma glutamyltransferase increased (19% each), and RBC count decreased (15%). 9 (35%) patients experienced grade ≥3 all-cause AEs after 12 mo (only 1 AE in >1 patient [Coronavirus infection]). Conclusions: Olutasidenib enabled LT CR/CRh in half of R/R m IDH1 AML patients with CR/CRh without transplant (longest response >54 mo). Multivariate analysis identified relapsed (vs refractory) AML and female sex but not baseline TI or molecular factors as a significant predictor of LT response with olutasidenib. Clinical trial information: NCT02719574 . Patients with LT response. DOR Group Patients, n (%) >12 mo 26 (100) >24 mo 19 (73) >36 mo 15 (58) >48 mo 5 (19)