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Original Articles

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

, , , , , & show all
Pages 3219-3225 | Received 16 Feb 2021, Accepted 12 Jul 2021, Published online: 27 Jul 2021
 

Abstract

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.

Acknowledgments

The authors thank Kelly J. Norsworthy, MD for sharing her experience, and advice in the development of this study protocol. The work for the current manuscript was completed while the primary author was a pharmacy resident at The Johns Hopkins Hospital.

Disclosure statement

No potential conflict of interest was reported by the author(s).

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