Localized Chemotherapy and Immunotherapy Best Practice for Glioblastoma

John Hopkins University researchers have found that localized chemotherapy – as opposed to systemic treatment – could help preserve immune system function when immunotherapy will also be used to treat glioblastoma. This research on the aggressive form of brain cancer was conducted in mice models, and the results were published in the journal, Science Translational Medicine.

“We understand that our research was done in a mouse model and not in humans, but our evidence is strong that systemic chemotherapy alters the immune system in a way that it never fully recovers,” said Dr. Michael Lim, associate professor of neurosurgery and director of brain tumor immunotherapy at the Johns Hopkins University School of Medicine, and member of the Johns Hopkins Kimmel Cancer Center. “With aggressive cancers like glioblastoma, it is important that we don’t handicap the defenses we may need to add alternative treatments, such as immunotherapy, to chemotherapy.”

Glioblastoma is the most common, and most aggressive, form of brain cancer, with the average patient surviving just one year after they receive a diagnosis. Like many other solid tumor types, glioblastoma is often treated using chemotherapy, radiation and surgical removal of the tumor.

In an effort to improve survival for patients with glioblastoma, neurosurgeons are turning to experimental immunotherapies. However, traditional systemic cancer therapies – such as chemotherapy – could weaken a patient’s immune system, thereby reducing the chances that immunotherapy will be effective for them.

Cancer clinical trials are increasingly looking to combine the standard of care for cancer with immunotherapy, making it necessary to better understand how these treatments function together. To determine whether localized or systematic chemotherapy are more compatible with new immunotherapies, Lim and his team tested these approached in mice.

The researchers dosed a group of mice with glioblastoma with the immunotherapy drug, anti-PD-1, and then treated the mice with chemotherapy, either directly to the brain or systemically throughout the whole body. After two weeks, the researchers counted the number of T cells present in blood samples taken from the mice, in order to assess immune system function.

The mice who were treated used systemic chemotherapy had lower levels of these lymphocytes, compared to those given the targeted therapy. The localized chemotherapy, in combination with immunotherapy, also improved survival to approximately 80 percent after 100 days; this is compared to 50 percent for mice given systemic chemotherapy and immunotherapy.

A number of clinical trials are currently being conducted to assess the effectiveness of immunotherapy for patients with glioblastoma. The current study could help guide these and future trials, to ensure that chemotherapy ad immunotherapy are being optimally used in combination.