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The use of dexamethasone may reduce the effectiveness of immune checkpoint inhibitors in patients with glioblastoma

CONCLUSIONS: Among glioblastoma patients who received immune checkpoint inhibitors, those who received corticosteroid dexamethasone at baseline for cerebral edema had significantly worse overall survival.

Journal of published research: Clinical cancer research, Journal of the American Association for Cancer Research

Author: David A. Reardon, MD, Clinical Director, Neuro-Oncology Center, Dana-Farber Cancer Institute, Boston

Background: “Dexamethasone is a potent corticosteroid and is often prescribed to patients with glioblastoma to treat symptoms associated with cerebral edema and swelling of the brain,” said Riadon. “Cerebral edema is a common but potentially life-threatening complication in patients with glioblastoma, and treatment with corticosteroids may help reduce inflammation in the brain,” he adds. It was.

Historically, patients with glioblastoma have been empirically treated with dexamethasone in the absence of symptoms, and many clinicians have long-term steroids because of concerns that patients may begin to develop edema. I’m prescribing.Our study examined that paradigm of clinical practice, especially in the era of immunotherapy, and whether there are negative results associated with the use of dexamethasone among patients with glioblastoma treated with immune checkpoint inhibitors. Designed to determine if.. “

Dr. David A. Riadon, MD, Clinical Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute

Study Methods and Results: Reardon et al. Evaluated the effect of co-administration of dexamethasone and an immune checkpoint inhibitor (anti-PD-1 therapy) in a syngeneic mouse glioblastoma model.

In an immune-sensitive mouse model that essentially responds to immune checkpoint inhibition, researchers found that adding dexamethasone to anti-PD-1 therapy resulted in a dose-dependent decrease in survival.

In addition, in immunoresistant mouse models, where riadon was pointed out to be more representative of human glioblastoma, addition of dexamethasone to anti-PD-1 or anti-PD-1 and radiation therapy also reduced survival. ..

“Preclinical studies have shown that steroids also have a significant adverse effect on the effectiveness of anti-PD-1 therapy in immunosensitivity models that overestimate the benefits of immune checkpoint inhibition in patients with glioblastoma.” Said Reardon.

Next, the researchers found that all 181 glioblastoma patients treated with either anti-PD-1 or anti-PD-L1 therapy at the Dana-Farber Cancer Institute diagnosed before April 1, 2019. Survival data was analyzed.

This patient population was heterogeneous and patients were treated through clinical trials or on the basis of compassionate use. About 76% were treated for recurrence and about 24% were treated for a new diagnosis. Of these 181 patients, about 35 percent were taking dexamethasone at baseline.

Riadon et al. Used multivariate analysis to assess the potential adverse effects of dexamethasone, and among 163 patients, disease setting (newly diagnosed and recurrence), tumor volume at the start of treatment, Adjusted for various factors such as age and extent of resection. There was fully annotated data on the relevant prognostic factors.

Patients treated with dexamethasone had about twice the risk of death compared to patients who did not take dexamethasone at baseline.

In addition, baseline use of dexamethasone was the most strongly identified negative risk factor for overall survival.

Author’s comment: “Our results should strive to avoid dexamethasone among patients with glioblastoma treated with immunotherapy, and if corticosteroids are clinically needed, these drugs It suggests that you need to use it with caution, “Riadon said.

“In addition, our results emphasize the need to decisively investigate other strategies for the treatment of cerebral edema that do not have such widespread anti-inflammatory effects.”

Research Limits: Research limits include the retroactive nature of clinical analysis. In addition, in preclinical studies, researchers only evaluated the effect of dexamethasone on the efficacy of anti-PD-1 treatment.

“It has not yet been evaluated whether the same observations will be made with other immunomodulatory checkpoint-targeted drugs or other immunotherapeutic treatments such as vaccines, adoptive cell therapies, and genetically engineered oncolytic viruses,” Riadon said. He said.

Funding and Disclosure: This study was sponsored by the Jennifer Oppenheimer Cancer Research Initiative.

Ben and Catherine Ivy Foundation; Hope to be 5K Beach Thing annually for brain tumor research. And Bike Attone’s Pan-Mass Challenge to raise money for the Dana-Farber Cancer Institute. This study was also funded by the National Institute of Health.

Source:

American Association for Cancer Research

The use of dexamethasone may reduce the effectiveness of immune checkpoint inhibitors in patients with glioblastoma

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