THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



IL-1 antagonists may have role in cancer fight

hench-lecture
Charles Dinarello, MD

Anakinra, an interleukin antagonist commonly used in the treatment of rheumatoid arthritis, is also used for other inflammatory diseases and recently has been studied as a treatment with chemotherapy for some cancers, according to Charles Dinarello, MD, who presented the Rheumatology Research Foundation Philip Hench, MD Memorial Lecture on Monday.

Evidence of a role for anakinra in cancer therapy is growing as the IL-1 receptor blocker (IL-1Ra) is being studied in acute myelogenous leukemia, colorectal cancer, prostate cancer, and multiple myeloma, said Dr. Dinarello, Professor of Medicine and Immunology at the University of Colorado School of Medicine, and Professor of Experimental Medicine at Radboud University in the Netherlands.

Anakinra was approved for the treatment of rheumatoid arthritis in 2002 and subsequently approved for other diseases. IL-1Ra blocks the IL-1 receptor and inhibits both IL-1 beta and IL-1 alpha. In addition to RA, an increasing number of common inflammatory diseases are responsive to anakinra, including osteoarthritis, gout, and macrophage activation syndrome.
In cancer patients, IL-1 promotes angiogenesis and tumor invasiveness, and there is evidence that it suppresses the immune response to cancer, Dr. Dinarello said.

IL-1 beta has been shown in hematopoietic cancer cells, including acute myelogenous leukemia, multiple myeloma, Hodgkin’s disease, and B-cell leukemias. IL-1 alpha has been shown in mesenchymal epithelial cancer cells, including breast, prostate, lung, colon, and pancreatic cancers and melanoma, he said.

“All healthy mesenchymal and epithelial cells contain the IL-1 alpha precursor, and normal platelets contain IL-1 alpha. The IL-1 precursor is active and upon cell death, IL-1 alpha is released and it triggers immediate inflammation,” he said.

Other IL-1 receptor antagonists are being used in trials to treat other diseases, such as canalinumab, which neutralizes IL-1 beta, rilonacept, which also neutralizes IL-1 beta, and xilonix, which neutralizes IL-1 alpha.

A recent phase 3 study of the use of xilonix with chemotherapy in patients with end-stage metastatic colorectal cancer showed increased overall survival in patients who responded to xilonix.

Overall survival in patients with advanced colorectal cancer who received four biweekly infusions of xilonix was 4.2 months in patients who did not respond to xilonix versus 11.5 months in those who did, Dr. Dinarello said.

Anakinra has been used to treat pancreatic and breast cancer, acute gout, macrophage activation syndrome, pre-multiple myeloma, idiopathic pericarditis, Kawasaki disease, post-myocardial heart failure, and decompensated heart failure.

Canakinumab has been used to treat gout and cardiovascular events in patients at high risk for cardiovascular events. Rilonacept has been used to treat progressive kidney failure. In addition to advanced colorectal cancer, xilonix has been used to treat psoriasis and type 2 diabetes.

In addition to his own work, Dr. Dinarello has trained more than 50 investigators, with many of them considered experts in their various fields. The Institute for Scientific Information listed Dr. Dinarello as the world’s fourth most-cited scientist during the 20-year period from 1983-2002.