359: Fatal Differentiation Syndrome Secondary to Menin Inhibitors: A Case Series

Hanmandlu, Ankit; Cuenca, John; Wegner, Robert; Botdorf, Joshua; Nates, Joseph L.; Reddy, Dereddi Raja

doi:10.1097/01.ccm.0000907164.42526.85

Cited by 2 publications

(1 citation statement)

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“…There are currently no published clinical trial data on the incidence of DS with the other menin inhibitors in development. However, KO-539 was placed on partial clinical hold due to adverse events of differentiation syndrome, and there was a recent case series reporting fatalities due to DS in two patients that received treatment with an unknown menin inhibitor [105,106]. The partial clinical hold for KO-539 was removed once adequate safety monitoring was implemented for monitoring of DS [107].…”

Section: Menin Inhibitorsmentioning

confidence: 99%

Differentiation Syndrome in Acute Leukemia: APL and Beyond

Woods,

Norsworthy

2023

Cancers

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Differentiation syndrome (DS) is a frequent and potentially life-threatening clinical syndrome first recognized with the advent of targeted therapeutics for acute promyelocytic leukemia (APL). DS was subsequently observed more broadly with targeted therapeutics for acute myeloid leukemia (AML). DS is typically characterized by fever, dyspnea, hypotension, weight gain, pleural or pericardial effusions, and acute renal failure. The incidence in patients with APL ranges from 2 to 37%, with the wide variation likely attributed to different diagnostic criteria, use of prophylactic treatment, and different treatment regimens. Treatment with corticosteroids +/- cytoreductive therapy should commence as soon as DS is suspected to reduce DS-related morbidity and mortality. The targeted anti-leukemic therapy should be discontinued in patients with severe DS. Here, we discuss the pathogenesis of DS, clinical presentations, diagnostic criteria, management strategies, and implementation of prospective tracking on clinical trials.

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Section: Menin Inhibitorsmentioning

confidence: 99%