Ivosidenib or Enasidenib Combined with Intensive Chemotherapy in Patients with Newly Diagnosed AML: A Phase 1 Study

Ivosidenib or Enasidenib Combined with Intensive Chemotherapy in Patients with Newly Diagnosed AML: A Phase 1 Study

In the April 1, 2021 edition of the Journal Blood, investigators reported on Ivosidenib and enasidenib utility in combination with intensive chemotherapy in newly diagnosed acute myeloid leukemia. Ivosidenib and enasidenib are small molecule inhibitors of isocitrate dehydrogenases 1 and 2, respectively.  Their efficacy has been well evaluated and documented in mutant IDH1 and IDH2 in the relapsed / refractory setting for acute myeloid leukemia.  The investigators report on a phase 1 clinical trial, evaluating the safety and efficacy of these 2 agents combined with intensive chemotherapy in patients with newly diagnosed mutated IDH1/2 acute myeloid leukemia.

Ivosidenib was administered at 500 mg daily and enasidenib was administered at 100 mg daily.  The drugs were well tolerated with consistent safety profiles. The frequency of Ivosidenib differentiation syndrome was low given concurrent utilization of cytotoxic chemotherapy. 

For patients who are treated with ivosidenib, QT interval prolongation was similar from monotherapy studies.  There was a notable increase in total bilirubin, but per the authors, this had little clinical impact on patients.  In patients treated with ivosidenib , n=60 patients, or enasidenib , n=91 patients, end of induction complete remission, rates were 55% and 47%, respectively and CR/CR incomplete neutrophil or platelet recovery rates were 72% and 63%, respectively.  In patients with a best overall response of CR/CRi/CRp , n=16-41 patients, 39%, receiving ivosidenib had IDH1 mutation clearance and 15 of 64 patients, 23%, receiving enasidenib had clearance of their IDH2 mutation.  These were confirmed by digital polymerase chain reaction. The investigators also noted that 16 of 20 patients, 80% and 10 of 16 patients, 63%, respectively, became negative for measurable residual disease by multiparameter flow cytometry.

https://ashpublications.org/Blood/article/137/13/1792/464087/Ivosidenib-or-enasidenib-combined-with-intensive

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