First Targeted Therapy Approved for R/R AML With IDH1 Mutation


The FDA approved the first targeted therapy for adults with relapsed or refractory acute myeloid leukemia with an IDH1 mutation. In addition, FDA also approved a companion diagnostic to be used to detect the specific mutations in the IDH1 gene.

Adults with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation now have a targeted therapy available to them. The FDA approved ivosidenib (Tibsovo from Agios Pharmaceuticals) to be used in combination with the RealTime IDH1 Assay, a companion diagnostic that the FDA approved the same day. The diagnostic test can detect specific mutations in the IDH1 gene in people with AML.

According to Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, ivosidenib is associated with complete remission in some patients.

“Tibsovo is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH1 mutation,” Pazdur said in a statement.

IDH1 mutation affects just 6% to 10% of patients with AML and the mutation blocks normal blood stem cell differentiation.

The therapy was approved based on an open-label, single-arm, multicenter dose-escalation and expansion trial of 174 patients. Almost two-thirds (63%) of patients were refractory to previous therapy and patients had received a median of 2 prior anticancer therapies. The trial found that 57 patients (32.8%) achieved complete remission (CR) and complete remission with partial hematologic improvement (CRh). The median duration of CR+CRh was 8.2 months.

The most common side effects of ivosidenib were fatigue (39%), increase in white blood cells (38%), joint pain (36%), diarrhea (34%), shortness of breath (33%), swelling in the arms or legs (32%), nausea (31%), pain or sores in the mouth or throat (28%), irregular heartbeat (26%), rash (26%), fever (23%), cough (22%), and constipation (20%).

“AML patients who relapse or are refractory to available therapies have few, if any, treatment options,” Hagop M. Kantarjian, MD, professor and chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said in a statement. “The clinical study demonstrated that Tibsovo has the potential to deliver strong, durable responses as a single agent and can help patients achieve and maintain transfusion independence. IDH inhibitors represent a new class of noncytotoxic, targeted therapies for AML patients with IDH mutations.”

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