Predicting side-effects and cancer's return in patients treated with immunotherapy by novel experimental test

A single research test has the potential to predict which patients treated with immunotherapies –which harness the immune system to attack cancer cells – are likely to have their cancer recur or have severe side effects, a new study found. Published online in Clinical Cancer Research, the study revolved around the set of immune system signaling proteins called antibodies that recognize invading bacteria, viruses, and fungi. These blood proteins are designed to glom onto and inactivate specific bacterial and viral proteins, but in some cases "autoantibodies" also react to the body's "self" proteins to cause autoimmune disease.

The researchers obtained blood samples from more than 950 patients enrolled in one of two Phase 3 randomized controlled trials of adjuvant checkpoint inhibitors in patients with advanced melanoma. Tumors in these patients had been surgically removed and blood samples collected before they received any treatment. The new test employs a microchip with 20,000 proteins attached in specific spots. When an antibody recognizes any of the proteins present in a blood sample, those spots glow with the signal intensifying as the concentration of antibody increases.

Based on the newly identified panel of autoantibodies, and using statistical modeling, the team developed a score-based prediction system for each treatment used. Patients with a high autoantibody recurrence score were found to have quicker disease return than those with a lower score according to the researchers and patients with higher pre-treatment autoantibody toxicity scores were significantly more likely to develop severe side effects than those with lower scores.

"That we identified 283 autoantibody signals shows that the biological phenomena underlying recurrence and toxicity are complex, and cannot be driven one or two biomarkers" said the researchers.

Reference:

Paul Johannet et al,Baseline serum autoantibody signatures predict recurrence and toxicity in melanoma patients receiving adjuvant immune checkpoint blockade,Clinical Cancer Research