The FDA recently approved ivosidenib (Tibsovo, Agios Pharmaceuticals) for patients with newly-diagnosed acute myeloid leukemia (AML) with IDH1 mutation, as detected by an FDA-approved test.

The indication is for patients aged 75 or older and for whom intensive chemotherapy is not an option due to comorbidities.

Lab test. Source: Getty

“Despite several new AML medicines approved in the last two years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities,” Chris Bowden, MD, chief medical officer at Agios, said in a press release. “With today’s additional Tibsovo approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options. In addition, we are continuing our work to expand the utility of Tibsovo in newly diagnosed AML patients in ongoing phase 3 trials in combination with both intensive chemotherapy and azacitidine.

The FDA based the approval of ivosidenib on an open-label, single-arm trial of patients (n = 28) with newly-diagnosed AML with an IDH1 mutation. Researchers enrolled patients who were at least 75 years old or who met at least one of the following criteria:

• baseline Eastern Cooperative Oncology Group performance status of ≥ 2;

• severe cardiac or pulmonary disease;

• hepatic impairment with bilirubin > 1.5 times the upper limit of normal; or

• creatinine clearance < 45 mL/min.

Most patients (79%) had therapy-related AML or AML with myelodysplasia-related changes. Researchers administered ivosidenib orally at 500 mg until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation. Two patients went on to receive stem cell transplantation after ivosidienib therapy.

Overall 42.9% of patients achieved complete remission or complete remission with partial hematologic recovery (95% CI, 24.5-62.8). Of the 17 transfusion-dependent patients, 7 (41.2%) achieved transfusion independence lasting at least 8 weeks.

The most common adverse events included diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome and myalgia.

Ivosidenib has a boxed warning for the risk of differentiation syndrome.