Dr. O'Reilly on Resistance to Immunotherapy in Pancreatic Cancer

Eileen M. O’Reilly, MD, associate director for Clinical Research, David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center, discusses resistance to immunotherapy in patients with pancreatic cancer.

According to O’Reilly, many in the field consider pancreatic cancer to be an “immune-privileged” tumor. The effector T cells are typically either absent or present in very low levels in the tumor microenvironment. The immune cells that are present are, instead, regulatory or suppressive.

The goal, says O’Reilly, is to try and alter the tumor microenvironment to allow effector T cells in and to allow immunotherapy drugs in, in order to overcome some of the inherent resistance that has been regularly observed. There are some strategies out there that combine single-agent checkpoints, though they have limited impact. Some research has also looked at combining checkpoint drugs with antibodies that alter the microenvironment.

There are still several ongoing trials looking at the efficacy of various immunotherapy agents to treat patients with pancreatic cancer. A phase I/II open-label study is currently investigating the safety and efficacy of nivolumab (Opdivo) as a single agent and in combination with ipilimumab (Yervoy) in several different tumor types, one of which is pancreatic adenocarcinoma. Another trial is studying the side effects and best dose of ipilimumab when given together with gemcitabine hydrochloride in treating patients with stage III/IV or recurrent pancreatic cancer that cannot be removed by surgery. Both ipilimumab and gemcitabine hydrochloride can work in their own respective ways to either block or kill tumor cells. Thus, the idea of combining the 2 is to see if, together, they can kill more tumor cells more effectively.