Use of the Steroid Dexamethasone May Reduce Responses to Immunotherapy Among Patients With Glioblastoma

Steroid is often used to prevent swelling in the brain, but may have “detrimental effect” on treatment with immune checkpoint inhibitors.

Among patients with glioblastoma who were being treated with an immune checkpoint inhibitor, those who were receiving the steroid dexamethasone at the initiation of their immunotherapy treatment had a worse prognosis, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research. 

“Our results suggest that we should try to avoid dexamethasone among patients with glioblastoma who are treated with immunotherapy, and if corticosteroids are clinically required, we should use these drugs judiciously,” said David A. Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston and an author of the study.

Glioblastoma is a malignant tumor that begins in the brain or spinal cord that tends to behave aggressively. Standard treatments for glioblastoma include surgery, chemotherapy, and radiotherapy.  Strategies using the type of immunotherapy known as immune checkpoint inhibition are being investigated in clinical trials among patients with glioblastoma. Dexamethasone is often prescribed to prevent or control cerebral edema, or swelling in the brain. 

“Historically, patients with glioblastoma have been empirically treated with dexamethasone, even without symptoms, with many clinicians prescribing steroids for prolonged periods of time, out of a concern that patients may start to develop edema,” Reardon continued. “Our study was designed to look at that paradigm of clinical practice, particularly in the immunotherapy era, and determine if there could be negative consequences associated with dexamethasone use among patients with glioblastoma treated with immune checkpoint inhibitors.”

In experiments with laboratory mice, Reardon said, adding dexamethasone to anti-PD-1 treatment, an immune checkpoint inhibitor, resulted in reduced survival in a dose-dependent manner. 

“In our preclinical studies, we found that steroids had a significant detrimental effect on the efficacy of anti-PD-1 therapy, even in an immunosensitive model, which over-predicts the benefit of immune checkpoint blockade in glioblastoma patients,” said Reardon.

The researchers also analyzed data from patients receiving anti-PD-1 or anti-PD-L1 therapy to evaluate the potential detrimental effects of dexamethasone, considering a variety of factors. Compared with patients who were not taking dexamethasone at baseline, patients treated with dexamethasone had roughly twice the risk of death.

Furthermore, use of dexamethasone at the beginning of immune checkpoint inhibitor treatment was the strongest identified negative risk factor for overall survival, Reardon said.