Innovative Approach to Understanding and Managing CAR T Cell Therapy Toxicities

Chimeric Antigen Receptor (CAR) T cell therapy is rapidly expanding beyond its initial use in treating blood cancers, now venturing into solid tumors and autoimmune diseases. As its applications grow, so does the importance of effectively managing associated side effects. Researchers, led by Dr. Kai Rejeski from LMU Klinikum, have introduced a new strategic framework, named IAGO—standing for Identification, Attribution, Grading, and Optimization—that aims to systematically address and mitigate these adverse effects.

Long-term side effects are increasingly evident as more patients enjoy extended survival post-therapy. These include neurological inflammation, persistent blood count abnormalities, secondary tumor development, and notably, infections. Dr. Rejeski explains that CAR T cells act as a "living drug," remaining in the body and continuously targeting immune cells like B cells, which can result in antibody deficiencies. Additionally, the initial lymphodepleting chemotherapy and ongoing cytopenias can weaken the immune system over time, heightening the risk for severe infections.

To improve patient outcomes, it is crucial to develop structured data collection and strengthen collaboration between university hospitals and community healthcare providers. This approach enables better detection, understanding, and treatment of side effects. An essential part of this has been the call for new standardized reporting systems for CAR T-associated infections, including details such as timing, type, severity, and whether prophylactic antibiotics were used.

The IAGO strategy offers a comprehensive method to tackle adverse effects: first, by identifying and describing side effects based on their frequency and severity; second, by establishing whether these effects are causally linked to the therapy; third, by implementing a standardized grading system to evaluate their clinical impact; and finally, by optimizing the management through innovative therapies. This structured approach aims to give healthcare professionals better control over CAR T cell therapy toxicities, ensuring safer and more effective treatments for patients.

This framework underscores the importance of consistent data collection, accurate reporting, and tailored treatment strategies as CAR T therapies become more widespread, highlighting the ongoing need for research and collaboration in this evolving field.

Source: https://medicalxpress.com/news/2025-07-framework-tackling-car-toxicities.html