On July 20, 2018, the US FDA approved ivosidenib (Tibsovo©, Agios Pharmaceuticals) for use in adult patients with relapsed or refractory acute myeloid leukaemia (AML) harbouring a susceptible IDH1 mutation as detected by an FDA-approved companion diagnostic (CDx) test, the Abbott RealTime IDH1 Assay.

Clinical Data

In an open-label, single-arm, multicenter clinical trial (AG120-C-001, NCT02074839), 174 adult patients with relapsed or refractory AML and an IDH1 mutation received oral ivosidenib 500 mg once daily with or without food until disease progression, unacceptable toxicity, or haematopoietic stem cell transplantation. The median duration of ivosidenib treatment was 4.1 (0.1-39.5) months and 12% (21/174) of treated patients underwent haematopoietic stem cell transplantation following ivosidenib treatment.

Efficacy parameters

Clinical activity, one of the co-primary endpoints of the study, was measured by the rate of complete remission (CR) plus complete remission with partial haematologic recovery (CRh). Furthermore, the investigators looked at the CR+CRh duration and the transfusion-dependence to -independence conversion rate. The AG120-C-001 study resulted in a 32.8% combined CR+CRh rate (95% CI, 25.8%-40.3%); the CR rate was 24.7% (95% CI, 18.5%-31.8%) and CRh rate was 8.0% (95% CI, 4.5%-13.1%). The median response duration was 8.2 months (95% CI, 5.6-12 months), and the time-to-response was 2 months (0.9-5.6 months).

At baseline, 110 patients were dependent on red blood cell (RBC) and/or platelet transfusions. During any 56-day post-baseline period, 41 (37.3%) of patients became independent of RBC- and platelet-transfusions. Moreover, at baseline 64 patients were independent of both RBC- and platelet-transfusions. During any 56-day post-baseline period, 38 (59.4%) of these patients remained transfusion-independent.

Common adverse reactions in ≥20% of ivosidenib-treated patients were fatigue, leukocytosis, arthralgia, diarrhoea, dyspnea, oedema, nausea, mucositis, QT prolonged, rash, pyrexia, cough, and constipation.

The CDx for detection of IDH1 mutations in AML patients to guide ivosidenib treatment, the Abbott RealTime IDH1 Assay, was approved on the same day.

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