Tibsovo Indication Expanded to Newly-Diagnosed Acute Myeloid Leukemia by FDA

May 3, 2019

Tibsovo (ivosidenib) is an isocitrate dehydrogenase1- inhibitor, originally approved in 2018.

The FDA has approved the expansion of indication for Tibsovo (ivosidenib) to include newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. It was originally indicated only for adult patients with relapsed or refractory AML. The new indication is only for adult patients with newly-diagnosed AML who are older than 75 years of age, or who have comorbidities that preclude use of intensive induction chemotherapy. 

The indication expansion is based on results from an open-label single-arm multicenter clinical trial of ivosidenib alone for newly-diagnosed AML with an IDH1 mutation. 

In the trial, 28 patients who were either at least 75 years of age or had a baseline Eastern Cooperative Oncology Group performance status greater than 2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin greater than 1.5 times the upper limit of normal or had a creatinine clearance less than 45 mL per minute. Twenty-two of the patients (79%) had therapy-related AML or AML with myelodysplasia-related changes. 

Efficacy in this trial was based upon: 

  • the rate of complete remission (CR) or complete remission with partial hematologic recovery (CRh), 

  • the duration of CR+CRh, 

  • conversion rate from transfusion dependence to transfusion independence

Of these patients, 42.9% (12 patients) achieved CR+CRh; 41.2% (7) of the 17 transfusion-dependent patients achieved transfusion independence lasting at least 8 weeks. 

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Ivosidenib is administered at 500 mg as two 250-mg tablets, ingested orally once daily with or without food until disease progression is seen or unacceptable toxicity occurs. Patients without disease progression or unacceptably toxicity should allow six months for any clinical responses to develop. Prescribing information for ivosidenib cautions patients to avoid consuming a high-fat meal before taking their medication. 

The most common adverse reactions reported in this trial, occurring in at least 25% of the patients, included diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia. 

The drug does not have any contraindications but does come with a boxed warning stating that patients treated with ivosidenib tablets have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Corticosteroid therapy and hemodynamic monitoring are to be initiated until symptom resolution if differentiation syndrome is suspected.

Full Prescribing Information