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

Oxana Megherea1, Carmen Janes2, Andrew Kowalski3

  • 1Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Leukemia & Lymphoma
|July 27, 2021
PubMed

Insights

Differentiation syndrome (DS) is a serious complication of IDH inhibitors used for acute myeloid leukemia. This study found a higher real-world incidence of DS in patients treated with these targeted agents.

Area of Science:

  • Oncology
  • Hematology
  • Pharmacology

Background:

  • Ivosidenib and enasidenib target mutant isocitrate dehydrogenase (IDH) enzymes.
  • These agents are used to restore normal cellular differentiation in acute myeloid leukemia (AML).
  • Differentiation syndrome (DS) is a known, potentially life-threatening complication associated with IDH inhibitors.

Purpose of the Study:

  • To determine the real-world incidence of differentiation syndrome (DS).
  • To characterize the clinical presentation of DS.
  • In patients with myeloid malignancies treated with IDH inhibitors.

Main Methods:

  • Multicenter, retrospective study design.
  • Analysis of 49 patients with myeloid malignancies treated with IDH inhibitors.
  • Evaluation for documented diagnosis and Montesinos criteria for DS.

Main Results:

  • 15 patients (31%) had a documented diagnosis of DS.
  • 8 patients (16%) met the Montesinos criteria for DS.
  • Common DS symptoms included dyspnea/hypoxia (56%), fever (56%), bone pain (44%), edema (39%), and effusions (33%).

Conclusions:

  • The real-world incidence of DS in patients treated with IDH inhibitors for myeloid malignancies appears higher than previously reported.
  • Understanding the incidence and characteristics of DS is crucial for managing patients on IDH inhibitors.
  • This study highlights the importance of monitoring for DS in this patient population.
Keywords:
Differentiation syndromeIDH inhibitorIDH-DSacute myeloid leukemiaenasidenibivosidenib

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