|The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Dexamethasone use was associated with shorter survival in a glioblastoma animal model and in a cohort of patients with glioblastoma treated with programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, according to the results of study presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).
“There is growing evidence that corticosteroids can exert detrimental effects on immunotherapy for cancer patients,” Bryan Iorgulescu, MD, FACP, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and presenter of the study, said. Dexamethasone is frequently administered to patients with glioblastoma, “but, there are limited data on how it affects systemic and intratumoral immune activity,” he said.
The study evaluated the effect of dexamethasone treatment on a glioblastoma mouse model and in an observational cohort of 181 patients with glioblastoma who received a PD-1/PD-L1 inhibitor.
The in vitro study treated immuno-sensitive syngeneic mice with glioblastoma with dexamethasone, an anti–PD-1 antibody, dexamethasone plus an anti–PD-1 antibody, or a control group of IgG daily for 8 days.
Overall survival (OS) was longest in the mice treated with an anti–PD-1 antibody alone, and was progressively shorter with increasing doses of dexamethasone. Dexamethasone alone resulted in similar OS rates as the control group. However, OS was not affected when dexamethasone was given prior to the anti–PD-1 antibody.
Similar results were observed when the mice were immunoresistant or when treated with radiotherapy concurrent with the dexamethasone and anti–PD-1 antibody.
Analysis of mouse tissues demonstrated that dexamethasone decreased systemic lymphocytes, intratumoral CD4-positive lymphocytes, and reduced T-cell production of interferon-γ. Dexamethasone also induced apoptosis of multiple types of immune cells.
Among the cohort of patients with glioblastoma, shorter OS was significantly associated with dexamethasone treatment in a dose-dependent manner (P ≤.005).
Dr Iorgulescu concluded that these data “reinforce that dexamethasone use should be minimized for brain tumor patients being considered for checkpoint inhibitor therapy or other immunotherapies.”
Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.
Iorgulescu B. Preclinical mechanistic and clinical evaluation of the corticosteroid dexamethasone’s detrimental effects on immune checkpoint blockade in glioblastoma cancer. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 209. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.