Olutasidenib (Rezlidhia) demonstrated sustained relapse-free survival as maintenance therapy for patients with IDH1-mutated acute myeloid leukemia (AML) who achieved complete remission or complete remission with incomplete hematologic recovery following induction therapy, according to findings from a phase 2 trial presented at the 2025 EHA Congress.
The study enrolled 18 patients with a median treatment duration of 19.6 months (range, 9.5-42.3) and median follow-up of 36.3 months (range, 27.3-41.7). Results showed the 4-month relapse-free survival rate was 83%, with 12- and 24-month RFS rates of 71% (95% CI, 44%-87%) and 48% (95% CI, 23%-68%), respectively.
Clinical Efficacy and Patient Outcomes
The overall survival rates remained consistently high, with both 12- and 24-month OS rates reaching 89% (95% CI, 62%-97%). Notably, two patients with prior venetoclax exposure who entered the study in complete remission with incomplete hematologic recovery converted to complete remission or complete remission with partial hematologic recovery during olutasidenib treatment.
"Olutasidenib as a single agent demonstrated clinically meaningful activity as a switch maintenance strategy in a subset of [patients with] AML with CR/CRi and persistent minimal residual disease [of no more than] 0.01% after prior therapy," stated lead study investigator Andrew Wei, MBBS, PhD, and colleagues. "This analysis supports the potential benefit of switching to olutasidenib upon response to therapy, with the goal of prolonging remission."
Study Design and Patient Population
Eligible patients required documented morphologic complete remission or complete remission with incomplete hematologic recovery and measurable minimal residual disease, defined as bone marrow IDH1 mutation levels no higher than 0.01%. Patients received olutasidenib at 150 mg orally twice daily in continuous 28-day cycles until disease relapse, unacceptable toxicity, initiation of alternative therapy, or withdrawal of consent.
The median age of enrolled patients was 68.5 years (range, 38-77), with one-third being female. Most patients (56%) had an ECOG performance status of 1, while 44% were classified as 0. The majority (94%) had primary de novo AML, with only one patient (6%) having secondary AML.
Regarding IDH1 mutation variants, R132C was most common (56%), followed by R132H (33%), and R132G/S (11%). The median bone marrow blast percentage at baseline was 2% (range, 1%-5%). Co-mutation burden was generally low, with 50% of patients harboring 1 to 3 co-mutations and 11% having 4 to 7 co-mutations.
Prior Treatment History
Thirty-nine percent of patients received two prior treatment regimens, while 50% received at least three prior lines of therapy. Common prior therapies included cytarabine (94%), daunorubicin/idarubicin (78%), hypomethylating agents (28%), and venetoclax (11%). Notably, 11% of patients had received hematopoietic stem cell transplantation, and 11% had been treated previously with olutasidenib.
Safety Profile
The safety profile in the maintenance cohort was consistent with other study cohorts, with adverse events being anticipated and manageable. All participants experienced at least one treatment-emergent adverse event, while serious treatment-emergent adverse events were reported in 33% of patients.
Grade 3 or 4 treatment-emergent adverse events were observed in 61% of patients (11/18), including febrile neutropenia, diarrhea, acute hepatitis, device-related infection, fall, increased hepatic enzymes, increased lipase, and pyoderma gangrenosum—each occurring in one patient. Importantly, no treatment-emergent adverse events or serious treatment-emergent adverse events resulted in treatment discontinuation.
The most commonly reported any-grade treatment-emergent adverse events included fatigue (33%), headache (33%), nausea (28%), constipation (22%), decreased neutrophil count (22%), and back pain (22%).
Regulatory Context
In December 2022, the FDA approved olutasidenib for adult patients with relapsed or refractory AML with a susceptible IDH1 mutation, as detected by an FDA-approved test. This approval was based on data from another cohort of the same phase 2 study (NCT02719574).
