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Optimal Chemotherapy Regimens Identified in Gastric Cancer

09/05/2017

By David Douglas

NEW YORK (Reuters Health) - A substantial minority of patients with relapsed or refractory acute myeloid leukemia (AML) show potentially deadly symptoms after treatment with enasidenib, according to a new analysis of data from an open-label trial.

As Dr. Amir T. Fathi told Reuters Health by email, "isocitrate dehydrogenase (IDH) inhibitors are increasingly studied as promising therapies for acute myeloid leukemia." In this study "of patients receiving the IDH2 inhibitor, enasidenib, as monotherapy for IDH2-mutated AML," he added, "we found that approximately 12% of patients experienced a differentiation syndrome, which was termed isocitrate dehydrogenase differentiation syndrome (IDH-DS)."

Dr. Fathi of Harvard Medical School, in Boston, and colleagues note that possible or probable IHD-DS was seen in 33 of 281 patients with relapsed or refractory AML being treated with enasidenib. The agent, they write in a report online January 18 in JAMA Oncology, "is a first-in-class, oral inhibitor of mutant isocitrate dehydrogenase 2 (mIDH2) proteins."

Patients ranged in age from 38 to 80; the most frequent manifestations of the syndrome were dyspnea, fever, pulmonary infiltrates, and hypoxia.

The median time to onset was 30 days, ranging from seven to 129 days. IDH-DS was significantly associated with fewer previous anticancer therapies at study entry (one versus two).

In 13 patients with concomitant leukocytosis, IDH-DHS was effectively managed with systemic corticosteroids. And although the enasidenib regimen was interrupted in 15 patients, permanent treatment discontinuation was not required.

Dr. Fathi stressed that "IDH-DS can manifest as a constellation of signs and symptoms which may include unexplained high fevers, respiratory symptoms, hypoxia, rash, and renal compromise. IDH-DS can be severe and potentially lethal without appropriate management, which includes the use of steroids and, if persistent and severe enough, a pause in therapy."

Dr. Shyam Ajay Patel, author of an accompanying editorial, told Reuters Health by email that "An important question that arises is whether the variant allele frequency of mIDH2 predicts enasidenib efficacy and toxicity."

Dr. Patel, of Stanford University School of Medicine, in California, concluded, "Studies on the correlation between the allelic burden of mIDH2 and treatment response may help guide clinical decision making."

The study was funded by Celgene Corporation and Agios Pharmaceuticals. Dr. Fathi reported ties to both companies.

SOURCES: http://bit.ly/2nbMpr5 and http://bit.ly/2E7k50T

JAMA Oncol 2018.

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