Immunotherapy for Low–Mutational Burden Prostate Cancer
Posted: Friday, May 15, 2020
Men who have prostate cancers with a high mutational burden have been thought to be good candidates for immunotherapy, as the response seems to depend on the presence of novel antigens caused by mutations (neoantigens). However, immunotherapy had not been considered a front-line treatment of low–mutational burden tumors, as they were thought to have lower levels of neoantigens due to fewer genetic mutations. Padmanee Sharma, MD, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues investigated the use of the monoclonal-antibody ipilimumab in metastatic castration-resistant prostate cancer. The results from this phase II trial were published in Science Translational Medicine.
“We were encouraged to see that prostate cancers with a low mutational burden do in fact express neoantigens that elicit T-cell responses that lead to favorable clinical outcomes,” said Dr. Sharma in an MD Anderson press release.
The study included 30 patients with metastatic castration-resistant prostate cancer. Analysis was performed on 29 patients, as they received between one and four doses of 3 mg/kg of ipilimumab every 3 weeks. Patients were divided into two groups based on radiographic progression-free and overall survival. A favorable response was classified as a progression-free survival of at least 6 months and an overall survival of at least 1 year.
Nine patients were classified as having a favorable response, whereas ten patients had an unfavorable response. The favorable group was found to have more cytotoxic T cells, memory T cells, and higher levels of interferon-γ signaling. Isolated T cells in the favorable-response group were found to respond to tumor neoantigens, whereas the ones in the unfavorable-response group were not.
“We found specific markers among a subset of patients with the greatest benefit, such as T-cell density and interferon-γ signaling, that may help improve our ability to select patients for treatment with checkpoint blockade,” commented study coauthor Sumit Subudhi, MD, PhD, also of MD Anderson.
Disclosure: For full disclosures of the study authors, visit stm.sciencemag.org.