NCCN Adds Olutasidenib to Guidelines for Relapsed/Refractory, IDH1-Mutant AML

Raul Rodriguez

Olutasidenib (Rezlidhia) has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology as a recommended targeted therapy for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) with an IDH1 mutation.¹

In December 2022, the FDA approved olutasidenib capsules for the treatment of adult patients with relapsed/refractory AML with a susceptible IDH1 mutation as detected by an FDA-approved test.²

“We are pleased that [olutasidenib] was quickly added to the NCCN Guidelines for AML, receiving important recognition as an appropriate treatment option for adult relapsed/refractory AML patients with an IDH1 mutation,” Raul Rodriguez, president and chief executive officer of Rigel, said in a press release. “Inclusion in the NCCN Guidelines for AML reinforces the strength of the data, which supports the safety and efficacy of [olutasidenib].”

Olutasidenib is an oral, small molecule, inhibitor of mutated IDH1 designed to bind to and inhibit mutant IDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells.

The FDA approval was supported by findings from the phase 1/2 Study 2102-HEM-101 trial (NCT02719574), in which treatment with olutasidenib induced a complete remission (CR) plus complete remission with partial hematologic recovery (CRh) rate of 35% (95% CI, 27%-43%), including a 32% CR rate and 2.7% CRh rate in 147 patients with relapsed/refractory AML with an IDH1 mutation. The median time to CR/CRh was 1.9 months (range, 0.9-5.6), and the median duration of CR/CRh was 25.9 months (95% CI, 13.5-not reached).

Additional findings demonstrated that 34% of patients who were red blood cell (RBC) and/or platelet transfusion dependent at baseline (n = 86) became RBC and platelet transfusion independent during any 56-day post-baseline period. Furthermore, 64% of patients who were RBC/platelet transfusion independent at baseline (n = 61) remained transfusion independent during any 56-day post-baseline period.

The open-label, single-arm, multicenter Study 2102-HEM-101 trial enrolled 147 adult patients with relapsed/refractory, IDH1-mutant AML. Mutational status was confirmed using the Abbott RealTime IDH1 Assay, which also received approval from the FDA as a companion diagnostic test.

Enrolled patients received 150 mg of oral olutasidenib twice daily. Treatment was continued until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (HSCT).

The median treatment duration was 4.7 months (range, 0.1-26). Sixteen patients (11%) underwent HSCT following olutasidenib.

The primary end points of phase 2 of the study included CR/CRh rate and 4-month relapse-free survival (RFS). Secondary end points included time to response, duration of response, event-free survival, overall survival, and RFS.

The most frequent adverse effects occurring in at least 20% of patients included nausea (38%), fatigue/malaise (36%), arthralgia (28%), constipation (26%), leukocytosis (25%), dyspnea (24%), fever, rash (24%), mucositis (23%), diarrhea (20%), and transaminitis (20%).

Per the FDA label, the agent should be taken on an empty stomach at least 1 hour before or 2 hours after a meal for at least 6 months, or until disease progression or unacceptable toxicity.

References

1. National Comprehensive Cancer Network® adds newly approved REZLIDHIA™ (olutasidenib) to Clinical Practice Guidelines in Oncology for acute myeloid leukemia. News release. Rigel Pharmaceuticals, Inc. January 18, 2023. Accessed January 18, 2023. https://prn.to/3CSk8gT
2. FDA approves olutasidenib for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation. News release. FDA. December 1, 2022. Accessed January 18, 2023. https://bit.ly/3Vr284u