Cancer Immunotherapy Experts Will Share Insights on Immune-Related Toxicities

Immunotherapies have revolutionized treatment of cancer, with multiple classes of newer immune-directed agents and cell-based treatments currently approved and in use in oncology practice, primarily in the case of hematologic malignancies. The potential of these innovative therapies, especially chimeric antigen receptor T-cell (CAR-T) therapies, is currently being explored for treating patients with autoimmune diseases.

At ACR Convergence 2024, Immunotoxicities from Cancer Treatments, to be held on Sunday, Nov. 17, from 1–2 p.m. ET in Ballroom A of the Walter E. Washington Convention Center, will include presentations by two cancer immunotherapy experts. Marco Ruella,MD, Assistant Professor of Medicine in the Division of Hematology/Oncology and the Center for Cellular Immunotherapies, and Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania, will focus on CAR-T toxicities and management. Laura Cappelli, MD, Associate Professor of Medicine and Oncology at the Johns Hopkins University School of Medicine, whose research focuses on the mechanisms, clinical features, and patient impact of rheumatologic toxicities of cancer immunotherapy, will speak about controversies in immune-related adverse event (irAE) management.

The session will be available on-demand to all registered ACR Convergence 2024 participants after the meeting through Oct. 10, 2025, by logging into the meeting website.

“Immunotherapies are certainly one of the most exciting treatments developed for cancer, as they provide the opportunity for complete remission for patients with cancers otherwise characterized by an extremely poor prognosis,” said Dr. Ruella. “Many patients have survived longer, but these therapies are also associated with new toxicities, which are not common or absent with standard chemotherapy and small molecule-based cancer therapies.”

These toxicities that involve the immune system, known as irAEs, include a broad spectrum of side effects. Dr. Ruella will give an overview of the irAEs associated with CAR-Ts, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenia, which can be prolonged.

There are many shared interests between immuno-oncology and rheumatology.

“These innovative cell-based immunotherapies are now starting to be applied for autoimmune diseases, including lupus, systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM),” Dr. Ruella noted.

Early studies of CAR-T therapy in autoimmune diseases have yielded promising results. In a small study of 15 patients with severe lupus, IIM, or SSc, a single infusion of CD19-targeted CAR-T cells alleviated or eliminated symptoms. As these therapies gain ground in the rheumatology space, the side effects of CAR-Ts become of greater interest to rheumatologists, because they might soon be able to offer these therapies to their autoimmunity patients, Dr. Ruella said.

He will provide an overview of the mechanism of action and processes involved in CAR-T cell production and therapeutic use, and outline how engineered CAR-T cells engage and kill target-positive cells, then proliferate, releasing cytokines. These cytokines then stimulate an inflammatory state involving myeloid and stromal cells, resulting in an exponential progression of inflammation, subsequently causing CRS, ICANS, other AEs, such as infection risk due to depletion of antibody-producing cells.

“Currently, we do not have enough data to make definitive statements about differences in AE profiles of CAR-Ts in cancer versus autoimmune disease,” Dr. Ruella said. “But the preliminary data in autoimmune disease seems to suggest that the safety profile of CAR-Ts may be more favorable in autoimmune disease. For instance, patients with autoimmune disease treated with CAR-Ts seem to recover their blood counts faster.”

The reasons for this have not been elucidated completely, he noted. He also issued the caveat that only a small number of autoimmune disease patients, around 15–20, have received these treatments thus far.

“When CAR-Ts are applied to patients, clinicians need to be aware of potentially new mechanisms of resistance and treatment failure or new toxicities,” Dr. Ruella noted.

To facilitate subsequent analyses and insights into potential resistance and toxicity mechanisms, it is important to prospectively bank samples, he added. Monitoring for potential long-term side effects is another consideration with immunotherapies.