Olutasidenib Continues to Induce Durable Remissions in IDH1-Mutant R/R AML


Updated findings from a phase 2 study have further confirmed the benefit of olutasidenib when used as a treatment option for patients with IDH1-mutant relapsed/refractory acute myeloid leukemia.

Treatment with olutasidenib (Rezlidhia) led to durable remissions in adult patients with IDH1-mutant relapsed/refractory (R/R) acute myeloid leukemia (AML), according to the phase 2 Study 2102-HEM-101 trial (NCT02719574).1

Olutasidenib is a potent, selective, oral, small-molecule inhibitor of mutant IDH1 that was previously granted FDA approval for use in patients with AML in December 2022.

Recent findings of the phase 2 trial were published in Blood Advances and showed treatment with olutasidenib to have an overall well-characterized safety profile with an adverse event (AE) profile largely representative of symptoms or conditions seen in patients with AML undergoing treatment. The agent also led to durable remissions and transfusion independence (TI) in patients with R/R AML, and the observed efficacy was clinically meaningful.

"Olutasidenib provides a welcome addition to the treatment of patients with refractory or relapse AML with IDH1 mutations. The high rate of responses, particularly complete responses, which are very durable, the very encouraging survival, and the favorable safety profile, make olutasidenib a valuable new agent for the management of these patients," Jorge E. Cortes, MD, director at the Georgia Cancer Center at Augusta University, told Targeted OncologyTM.

Within the pivotal cohort of the phase 2 registrational study, 153 adult patients with IDH1-mutant R/R AML were enrolled and administered oral olutasidenib monotherapy at 150 mg twice a day. The efficacy evaluable population included 147 patients with centrally confirmed mutant IDH1.

The median age of patients enrolled was 71 years (range, 32-87), and the median number of prior regimens was 2 (range, 1-7). Investigators assessed the primary end points of composite of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), maximum tolerated dose, dose limiting toxicities, and 4-month relapse-free survival. Secondary end points included safety, pharmacokinetics, time to response, duration of response (DOR), event-free survival, overall survival (OS), and relapse-free survival.2

Findings showed that treatment with olutasidenib demonstrated a 35% CR+CRh rate in patients with IDH1-mutant R/R AML (95% CI, 27.0-43.0). Among patients who achieved CR+CRh, 92% (47/51) were CR and most patients who achieved CR or CRh responded early, making for a median time to response of 1.9 months. The median duration of CR+CRh was 25.9 months (95% CI, 13.5-NE). and the median duration of CR was 28.1 months.

The median DOR was 11.7 months (95% CI, 6.9-25.9) with an overall response rate of 48% (95% CI, 40.0-56.7). Response rates were similar between patients who had and who had not received prior venetoclax (Venclexta). Moreover, the overall population had a median OS of 11.6 months (95% CI, 8.9-15.5). However, median OS was not reached in patients who achieved CR+CRh, and the estimated 18-month survival was 78%.

Another clinical benefit observed was conversion to TI, which was observed across all response groups. TI was achieved in 34% of patients given olutasidenib who were classified as dependent on red blood cell and/or platelet transfusions at baseline.

Regarding safety, olutasidenib was well characterized. Differentiation syndrome was observed in 14% of patients with 14 (9%) being grade ≥3 and 1 fatal case reported. However, differentiation syndrome was manageable in most cases using dose interruption and corticosteroids. AEs that were the most common were gastrointestinal and hematologic. However, most cases were manageable when using dose interruptions or modifications.

The grade 3/4 treatment-emergent AEs which occurred in 10% of patients or more included febrile neutropenia and anemia (20% each), thrombocytopenia (16%), and neutropenia (13%).

Overall, these data represent a therapeutic advance in a patient population that often has a poor-prognosis.

Rigel announces publication of REZLIDHIA™ (olutasidenib) phase 2 clinical results in blood advances. News release. Rigel Pharmaceuticals, Inc. February 2, 2023. Accessed February 8, 2023. https://prn.to/3Xldx5Q
de Botton S, Fenaux P, Yee KWL, et al. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML [published online ahead of print, 2023 Feb 1]. Blood Adv. 2023;bloodadvances.2022009411. doi:10.1182/bloodadvances.2022009411
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