Older adults with cancer respond just as well as younger patients to immune checkpoint inhibitors despite age-related immune system differences, according to a study by researchers from the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the Johns Hopkins Convergence Institute. The study was supported in part by the National Institutes of Health, including the National Cancer Institute's Specialized Programs of Research Excellence.
Most new solid tumor cancer diagnoses happen in people ages 65 or older, and overall, these patients have worse cancer treatment outcomes than their younger peers. The reasons for these differences are not entirely clear. Age-related changes that make the immune system less effective could make it harder for patients' immune systems to fight cancer cells. Newer immune system-boosting therapies may help, but questions remain about whether age-related immune changes might blunt the drugs' effects.
The new study, published April 21 in Nature Communications, bolsters evidence that lifesaving immune checkpoint inhibitors are effective across age groups despite age-related changes in the immune response. The study identifies some key differences in the immune response to these drugs in older patients compared with younger ones that may one day help clinicians further personalize therapies and boost treatment success.
Older patients do just as well, sometimes better than younger patients with immunotherapy treatments. We found clues about important pathways mediating the immune system response to immunotherapies in younger versus older patients that may help us improve the next generation of therapies or allow us to use current therapies in all patients more effectively."
Daniel Zabransky, M.D., Ph.D., senior author, assistant professor of oncology, Johns Hopkins University School of Medicine
The study examined immune cells and proteins they release called cytokines in the blood of about 100 patients treated with immune checkpoint inhibitors for cancer. About half of the patients were ages 65 or older. Both groups benefited from therapy equally, but there were differences in their immune responses and immune cells.
For example, T cells are the cells that help destroy damaged cells, bacteria or viruses. In response to an infection or other threat, groups of T cells specialize to eliminate that particular foe. Some T cells are considered "inexperienced" and remain on standby to respond to future threats. These inexperienced T cells in older patients looked like "they'd been around the block," Zabransky says, suggesting that they may be less ready to respond to threats such as cancer without additional treatments such as immune checkpoint inhibitors. These differences may make immune checkpoint inhibitors even more beneficial for older patients.
Next, Zabransky and his team want to look at differences in immune cells found inside tumors and compare them across age groups to see how they react to immunotherapies. They hope that by understanding age-related differences in immune responses to cancer therapies, they can either develop new cancer therapies better tailored to different age groups' needs or find new ways to combine existing treatments to improve care. It's imperative, he notes, to find ways to boost therapy effectiveness in older patients without triggering toxicities or other adverse events that can lead to poor outcomes.
"Right now, we give immune checkpoint inhibitors to patients in the same way without major consideration about how their age may influence how the immune system may recognize cancer cells," he says. "By better understanding age-related changes that we all experience over our lifespan, we hope to identify new strategies and personalize our therapies even further based on those important patient-level factors."
Other study authors were Chester Kao, Soren Charmsaz, Hua-Ling Tsai, Khaled Aziz, Daniel H. Shu, Kabeer Munjal, Ervin Griffin, James M. Leatherman, Evan J. Lipson, Yasser Ged, Jeannie Hoffman-Censits, Howard L. Li, Elsa Hallab, Madelena Brancati, Mari Nakazawa, Stephanie Alden, Christopher Thoburn, Nicole E. Gross, Alexei G. Hernandez, Erin M. Coyne, Emma Kartalia, Marina Baretti, Elizabeth M. Jaffee, Won Jin Ho, and Mark Yarchoan of Johns Hopkins. Researchers from Genentech Inc. and F. Hoffman-La Roche Ltd., also participated in the study.
Additional support for the study was provided by the Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Swim Across America, imCORE-Genentech, the MacMillan Pathway to Independence Award, the MD Anderson GI SPORE Career Enhancement Award from the National Cancer Institute and the Maryland Cancer Moonshot Research Grant.
How your diet and probiotics can improve vaccine effectiveness