Severe Treatment-Induced Arthritis Might Predict Cancer Progression in People on Checkpoint Inhibitors, Study Suggests

But, unharnessing the immune system can bring lots of unwanted side effects, too. As the immune system declares war on cancer cells, all that inflammation can do damage elsewhere in the body as well. People on checkpoint inhibitors might get a serious rash, diarrhea or other GI problems, lung inflammation, and in about 4% of people arthritis. These immune symptoms may be par for the course with this type of drug. But, new research raises the question, "Do some immune reactions offer a window into a patient's prognosis?"

A new study explores the question, but researchers say it's too soon to know for sure.

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The small study found that as treatment-induced arthritis severity increases, so does the risk that the cancer will progress. "But this is very preliminary data, based on a small group of people with a variety of cancers and treatment regimens. Rheumatologists need to study this issue more closely," Karmela Kim Chan, MD, tells SurvivorNet. Chan is a rheumatologist at the Hospital for Special Surgery in New York and co-author of the study.

Here's What Researchers Learned

The study tracked just 42 people. It's not enough people to influence the way doctors make treatment decisions, but it could lay the groundwork for larger studies that could make a difference.

In the study, researchers looked at people who developed arthritis while taking checkpoint inhibitors for cancer. They had several different types of cancer. Most of them had stage IV melanoma, lung cancer or renal cancer. They were taking several different types of checkpoint inhibitors, including those that block CTLA-4 (e.g. Yervoy), PD-1 (e.g. Keytruda, Opdivo, Libtayo), or PD-L1 (e.g. Tecentriq, Bavencio, Imfinzi).

Related: Checkpoint inhibitors before surgery could improve the odds for lung cancer patients

The researchers rated the severity of the patients' arthritis using the Clinical Disease Activity Index. This is a tool that rheumatologists use and it's more detailed than the way cancer doctors usually evaluate treatment-induced arthritis.

"Our study found that for every point increase in the clinical disease activity index, the risk of cancer progression increased by 11 percent," Chan says.

Not only did those whose cancer progressed have more severe arthritis, but they also developed arthritis sooner than those whose cancer didn't progress about two months after starting checkpoint inhibitors compared to four months for the others.

Dr. Geoffrey Oxnard explains how checkpoint inhibitors help the body fight lung cancer.

The people who had the most severe arthritis were more likely to have rheumatoid arthritis. That’s the kind that affects small joints, like those in your fingers and toes. Rheumatoid arthritis was most likely to develop in people taking PD-1 blockers alone as opposed to people taking other checkpoint inhibitors or a combination of them.

More Research Is Needed

Before oncologists can use this type of information to make treatment decisions, larger studies need to get the same results, Jeffrey Weber, MD, PhD, tells SurvivorNet. He is deputy director of NYU Langone Perlmutter Cancer Center. Future studies, he says, should compare those who develop arthritis to those who do not.

"This study compared progressors to non-progressors," Weber says. "The small number of patients, the fact that they were unlikely to be on a protocol with uniform follow up and timing of scans and disease evaluations, render this work impossible to interpret, and inappropriate as a basis for making clinical judgements."

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