FDA Approves Ivosidenib to Treat Myelodysplastic Syndromes With IDH1 Mutation

FDA Approves Ivosidenib to Treat Myelodysplastic Syndromes With IDH1 Mutation

The FDA has approved ivosidenib (Tibsovo) for adults with relapsed or refractory myelodysplastic syndromes (MDS), with a susceptible IDH1 mutation as detected via an FDA-approved test. The agency also approved the Abbott RealTime IDH1 Assay as a companion diagnostic test to identify patients eligible for ivosidenib.¹

“The novel use of targeted therapy across IDH-mutated cancers has become a powerful therapeutic option for patients within this molecularly defined subset,” Amir Fathi, MD, a hematologist, and medical oncologist at Massachusetts General Hospital, said in a press release. “This new indication in IDH1-mutated relapsed or refractory myelodysplastic syndromes reinforces the importance of mutational testing to inform treatment decisions and potentially improve patient outcomes.”²

Data Supporting the Decision

Findings from the AG120-C-001 trial (NCT02074839) support the approval. This open-label, single-arm trial included 18 patients with relapsed or refractory MDS and an IDH1 mutation.

IDH1 mutations were detected in the patient’s peripheral blood or bone marrow through either a local or central diagnostic test. They were then confirmed retrospectively with the Abbott RealTime IDH1 Assay.

Ultimately, 38.9% (95% CI, 17.3%-64.3%) of patients experienced a complete response (CR) following treatment. The median duration of CR was not estimable (range, 1.9-80.8+) and the median time-to-CR was 1.9 months (range, 1.0-5.6).

Additionally, among 9 patients who had previously been red blood-transfusion or platelet-transfusion dependent, 6 (67%) became independent within a 56-day post-baseline period. Further, 7 (78%) remained transfusion independent during that period.

Nursing Considerations

Patients in the trial received ivosidenib at a starting dose of 500 mg daily. This continued on a 28-day cycle basis until either disease progression, unacceptable toxicity, or, in the case of 1 patient, hematopoietic stem cell transplantation.

The oral agent can be taken with or without food. It should be taken at the same time every day and must be swallowed whole. It may not be split, crushed, or chewed. In addition, patients should not take ivosidenib with a high-fat meal, or a meal containing a high amount of butter or red meat.³

The most common adverse events (AEs) reported in the trial were similar to those seen in patients who are treated with ivosidenib for acute myeloid leukemia. These included gastrointestinal toxicities, such as diarrhea, constipation, mucositis, and nausea, arthralgia, fatigue, cough, myalgia, and rash. Ivosidenib may also cause QTc prolongation.

Of note, the prescribing label comes with a Boxed Warning for the risk of differentiation syndrome—which may be life-threatening or fatal. If differentiation syndrome is suspected, corticosteroid therapy should be initiated with hemodynamic monitoring until the symptom is resolved.

“I remember feeling confused trying to make sense of my diagnosis, what having an IDH1-mutation meant, and what options were available for my treatment plan,” Susan, a patient living with the disease, added in the press release. “The news of an FDA approval for a targeted therapy in IDH1-mutated MDS has given me a tremendous sense of gratitude and provides hope to patients like me who are living with this disease. I want to thank everyone who played a role in this major step forward for the MDS community.”

References

1. FDA approves ivosidenib for myelodysplastic syndromes. FDA. News release. October 24, 2023. Accessed October 24, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-myelodysplastic-syndromes?utm_medium=email&utm_source=govdelivery
2. Servier announces FDA approval of TIBSOVO® (ivosidenib tablets) for the treatment of IDH1-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). Servier. News release. October 24, 2023. Accessed October 24, 2023. https://servier.us/blog/servier-announces-fda-approval-of-tibsovo-ivosidenib-tablets-for-the-treatment-of-idh1-mutated-relapsed-or-refractory-r-r-myelodysplastic-syndromes-mds/
3. Tibsovo. Prescribing information; 2023 Servier Pharmaceuticals, LLC. Accessed October 24, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211192s011lbl.pdf