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6527 Background: Elderly patients with relapsed/refractory (R/R AML) are a special population that may elevate safety concerns, which must be balanced with clinical benefit. Olutasidenib (OLU), a targeted therapy for m IDH1 AML, was well tolerated in a registrational, Ph2, open-label, multicenter trial and, in the pivotal cohort, demonstrated complete remission (CR) or CR with partial hematologic recovery (CRh) in 35% of patients (age 32-87 years, y) for a median duration of 25.9 months. We evaluated safety and efficacy of OLU in the elderly subgroup (≥75y) with m IDH1 AML. Methods: In the Phase 2 trial, the pivotal cohort enrolled adults with R/R m IDH1AML. OLU was administered at 150 mg BID. Adverse events (AE) and lab values were collected at least monthly and graded based on the NCI CTCAE Version 4.03. Efficacy was based on response criteria of the International Working Group in AML (2003). Results: 153 patients received OLU monotherapy, 147 had centrally-confirmed mIDH1 AML, , and 45 were ≥75y (range 75-87) at study entry. Of the 45 elderly patients, 27 (60%) were male, 51% had ECOG=1, 16% had ECOG =2, 71% were relapsed, 29% had refractory AML, 58% had prior HMA, 11% received prior venetoclax, and none had prior stem cell transplant. Median bone marrow blasts were 43% (5-93). Genetic co-mutations included FLT3 in 9%, NPM1 in 20%, and TP53 in 2%. Grade 3 or 4 adverse events were reported in 45.8% of elderly patients; the most common were decreases in red blood cells (31%), platelets (13%) and neutrophils (10%) as well as febrile neutropenia (15%). AEs were consistent with published pivotal Phase 2 results, with no new safety signals. Deaths occurred in 19 patients due to disease progression (9), pneumonia (2), sepsis (2), GI haemorrhage (1), aortic stenosis (1), atrioventricular block (1), cardiac failure congestive (1), acute kidney injury (1) and other (1). The response to OLU therapy is summarized in the table. 31% of patients ≥75 y achieved CR/CRh; median time to CR/CRh was 1.5 mos (0.9-5.6) and median duration of CR/CRh was 25.9 mos (95%CI 7.4, not reached). Conclusions: Olutasidenib was generally well tolerated in elderly patients with R/R m IDH1AML and induced durable remissions. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with olutasidenib. Clinical trial information: NCT02719574 . Table: see text
Botton et al. (Sat,) studied this question.