In this episode of Hematology Pills, Dr. Marco Ruella, Prof. Robin Foà, and Dr. Filippo Milano dive into the challenges of CAR T-cell therapy resistance. They explore key resistance mechanisms, including T-cell dysfunction, the tumor microenvironment, and antigen loss, such as CD19 in relapsed ALL. Dr. Ruella discusses promising strategies to overcome these hurdles, like dual-targeting approaches, and highlights the importance of improving CAR T-cell product quality and monitoring in clinical settings. The episode also touches on the inflammatory side effects, like cytokine release syndrome (CRS) and neurotoxicity (ICANS), and their potential for enhancing the anti-tumor effect. Tune in for a deep dive into the future of CAR T-cell therapies and their evolving role in cancer treatment.