On the 2nd of May 2 2019, the FDA approved ivosidenib (Tibsovo®, Agios) as treatment for newly-diagnosed acute myeloid leukaemia (AML) patients ≥75 years old and AML patients with comorbidities precluding intensive induction chemotherapy. Patients should harbour a susceptible IDH1 mutation, as per the FDA-approved Abbott RealTime™ IDH1 Assay, to be legible for ivosidenib treatment.

Phase 1 data

The FDA approval was based on the phase 1, open-label, single-arm, multicentre AG120-C-001 trial (NCT02074839) investigating single-agent ivosidenib in 28 newly-diagnosed AML patients aged ≥75 years (median age 77 years [range, 64-87]) or patients with one or more comorbidities including a baseline Eastern Cooperative Oncology Group (ECOG) performance status ≥2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal (ULN), or creatinine clearance < 45 mL/min. Moreover. all patients were found to harbour an IDH1 mutation by the Abbott RealTime™ IDH1 Assay. Twenty-two (79%) had therapy-related AML or AML with myelodysplasia-related changes. Patients received ivosidenib-treatment until progression disease, the development of unacceptable toxicity, or haematopoietic stem cell transplantation (HSCT). The efficacy endpoints included the rate of complete remission (CR) or CR with partial haematological recovery (CRh), the duration of the CR/CRh response, and the conversion-rate from transfusion-dependence to  -independence.

Of the 28 enrolled patients, 12 (42.9%; 95% CI, 24.5-62.8) had a CR or CRh. Seven (41.2%) of the 17 transfusion-dependent patients became transfusion-independent for 8 weeks or longer. Two (7%) of the 28 patients underwent HSCT following ivosidenib.

Safety

Adverse reactions in at least 25% of patients included diarrhoea, fatigue, oedema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnoea, differentiation syndrome and myalgia. The ivosidenib prescribing information contains a Boxed Warning about the risk of life-threatening or fatal differentiation syndrome.

Full prescribing information Tibsovo®.