New Targeted Therapy for Myelodysplastic Syndromes

The FDA has approved the IDH1 inhibitor ivosidenib for a group of blood cancers harboring an IDH1 mutation. 

The U.S. Food and Drug Administration (FDA) has approved ivosidenib (Tibsovo) for the treatment of relapsed or treatment-refractory myelodysplastic syndromes (MDS) that harbor a mutation in the gene IDH1. 

Ivosidenib inhibits certain mutant forms of the enzyme IDH1. Normally, IDH1 is an important component of the process by which cells break down glucose to make energy. When IDH1 is mutated, it makes an atypical product called 2-hydroxyglutarate, which can damage DNA and alter the way genes are expressed, leading to cancer. A companion diagnostic test, the Abbott RealTime IDH1 Assay, was approved concurrently to identify IDH1 mutations in MDS cases. 

A microscope view of a bone marrow biopsy for myelodysplastic syndromes.

The approval was based on results from AG-120-C-001, a phase I, open-label, single-arm, multicenter trial that enrolled 18 patients with relapsed or treatment-refractory myelodysplastic syndromes that tested positive for an IDH1 mutation. Trial participants took oral ivosidenib once daily until disease progression, unacceptable toxicity, or undergoing a stem cell transplant. 

The overall response rate was 38.9%; all responses were complete responses. The median duration of response was not estimable. Of the nine patients dependent upon red blood cell and/or platelet transfusions at the start of the trial, six were able to go eight or more weeks without a transfusion during or after the trial. Of the nine patients who were not dependent upon transfusions at the start of the trial, seven remained transfusion-independent for eight or more weeks during or after the trial. 

The prescribing information for ivosidenib contains a boxed warning for differentiation syndrome, a potentially life-threatening inflammatory reaction that may involve fever, fluid buildup around the lungs, kidney failure, and other symptoms. 

Myelodysplastic syndromes are a group of cancers characterized by an overabundance of immature blood cells that do not develop properly into their mature forms, leading to fewer healthy blood cells. Incidence of MDS in the United States has been estimated between 5.3 and 13.1 individuals per 100,000 among different age groups, with incidence increasing with age.

The FDA rendered its decision on October 24, 2023.