Identifying Predictors for Immunotherapy Toxicities

Upal Basu Roy, MPH, PhD, LUNGevity Senior Director of Research

In recent years, immunotherapy, a treatment that enhances the body’s own immune cancer-fighting response, has been shown to be a very promising treatment option. Immunotherapy has proven effective for treating multiple cancer types, including some types of non-small cell lung cancer (NSCLC). Among these NSCLC patients, currently about 20% respond to the treatment.

Unfortunately, there may be toxicities, or side effects, of immunotherapy, and they are challenging to predict. Because immunotherapy works by taking the brakes off the immune system, every part of the body has the potential to be damaged by the overactive immune system. Many toxicities are mild or easily managed. However, some patients experience severe toxicities and cannot continue immunotherapy treatment.

Mehmet Altan, MD, assistant professor at the University of Texas MD Anderson Cancer Center, wanted to find a way to predict a patient’s risk of toxicity from immunotherapy treatment. “Immunotherapy is very exciting. It allows us to be able to celebrate multiple Thanksgivings and Christmases with patients,” explains Dr. Altan. “I believe that understanding the underlying causes of immunotherapy toxicities and developing better ways to select patients for treatment will improve the quality of life for our patients.”

In preliminary discussions, Dr. Altan and collaborators from UT Southwestern hypothesized that an amped-up immune system could be guided by naturally occurring self-antibodies, or antibodies targeting healthy tissue, to attack various parts of their own body and cause toxicity.

To dig deeper into this possibility, Dr. Altan and his team studied blood samples from patients with NSCLC.  Their results demonstrated that changes in immune cells correlated with immunotherapy toxicities and suggested that the team could be on the right track for predicting immunotherapy toxicity.

To continue this important work to determine if self-antibodies or immune cell activity could be used to predict a patient’s toxicity risk during immunotherapy, Dr. Altan applied for a three-year Career Development Award from LUNGevity and was awarded it in 2017.

“The LUNGevity award has been critical to my continued work on this project.  And I really appreciate the ability to discuss my research with superstar lung cancer researchers,” notes Dr. Altan. “The external mentorship, networking, and possible future collaborations have also been very helpful and exciting.”

His research is moving along swiftly. Already, his clinical trial to study self-antibodies and immune cells in blood samples from patients before and during immunotherapy treatment has enrolled approximately 65 patients in just eight months. “It is accruing well. We hope to have approximately 210 patients enrolled by the end of the study in 2020,” notes Dr. Altan.

In the meantime, he expects to have some preliminary results by the summer of 2019. Until then, Dr. Altan will continue to study how self-antibodies and immune cells contribute to immunotherapy outcomes for patients. “As we learn about toxicities caused by immunotherapy, we will be able to refine our toxicity management strategies to give patients better outcomes,” says Dr. Altan. “That is my goal, my team’s goal and LUNGevity’s goal. Together, along with other passionate researchers, I am confident we will get there.”

 

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Dr. Basu Roy is LUNGevity's Director of Translational Research Programs/Director of Patient FoRCe. Dr. Upal Basu Roy

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