Expert Perspectives: T-Cell Fitness and Its Role in CAR-T Treatment Planning

T-cell fitness plays a crucial role in the success of chimeric antigen receptor (CAR) T-cell therapy. Clinical data have shown that response rates improve when CAR T is used earlier in the treatment course. This is because repeated chemotherapy treatments can damage T cells, reducing their quality and effectiveness. When T cells are collected after multiple lines of chemotherapy, their ability to expand and attack cancer cells may be compromised. Therefore, prioritizing CAR T therapy earlier helps ensure that the collected T cells are more robust and functional, which increases the likelihood of a durable response.

Another important factor to consider is the use of bispecific antibodies, which have recently become available as treatments for certain types of lymphoma. These therapies work by engaging T cells to recognize and attack cancer cells, specifically targeting proteins like CD3 and CD20. However, there is concern that exposure to bispecific antibodies might cause T-cell exhaustion if the disease progresses soon after treatment. Exhausted T cells may be less effective when harvested for CAR T manufacturing, potentially leading to poorer outcomes. While this idea is largely theoretical at this point, it suggests caution when sequencing treatments to avoid compromising the quality of T cells used for CAR T.

Given these considerations, early referral for CAR T therapy is essential to maximize patient outcomes. Delaying CAR T in favor of multiple other therapies, including bispecific antibodies, risks collecting less fit T cells and reducing the chances of success. Early use of CAR T not only takes advantage of the cells’ better fitness but also aligns with evidence showing improved survival outcomes when CAR T is given sooner rather than later. Ultimately, careful treatment planning that considers T-cell health can improve the effectiveness of CAR T therapy in lymphoma patients.