Real-world assessment of isocitrate dehydrogenase inhibitor-associated differentiation syndrome

Leuk Lymphoma. 2021 Dec;62(13):3219-3225. doi: 10.1080/10428194.2021.1957868. Epub 2021 Jul 27.


Ivosidenib and enasidenib are targeted agents that inhibit mutant isocitrate dehydrogenase (IDH) enzymes, restoring normal cellular differentiation in affected acute myeloid leukemia patients. Both agents carry a risk of differentiation syndrome (DS), a potentially life-threatening complication. In this multicenter, retrospective study we sought to determine the real-world incidence and characterize DS in patients with a myeloid malignancy treated with an IDH inhibitor. Of 49 total patients, 15 patients (31%) had a documented diagnosis of DS and 8 patients (16%) met the criteria of DS by Montesinos, et al. The most common signs and symptoms of DS were dyspnea/hypoxia (56%), unexplained fever (56%), bone pain/arthralgia (44%), edema/weight gain (39%), and pleural/pericardial effusions (33%). Our study reports a higher real-world incidence of DS in patients treated with IDH inhibitors for myeloid malignancies than previously reported.

Keywords: Differentiation syndrome; IDH inhibitor; IDH-DS; acute myeloid leukemia; enasidenib; ivosidenib.

Publication types

  • Multicenter Study

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Enzyme Inhibitors / adverse effects
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Leukemia, Myeloid, Acute* / diagnosis
  • Mutation
  • Retrospective Studies
  • Syndrome


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Isocitrate Dehydrogenase