Expert Insights in Additional CAR T Therapies for Third-Line R/R LBCL

There are 3 CAR T-cell therapies approved for use in the third-line treatment of LBCL, each with comparable efficacy but different characteristics. These therapies differ primarily in their co-stimulatory domains, which influence both the expansion of T cells and their toxicity profiles. Products with a CD28 co-stimulatory domain tend to expand more quickly, which can lead to higher rates of cytokine release syndrome and neurotoxicity. In contrast, those with a 4-1BB co-stimulatory domain expand more slowly, often resulting in lower acute toxicity but potentially prolonged B-cell aplasia.

The choice of CAR T product is often driven by institutional experience, turnaround time, and patient-specific considerations. Some centers may be more familiar with one product over another, influencing their comfort with managing adverse effects and outcomes. Additionally, manufacturing time plays a role; certain therapies have shorter vein-to-vein intervals, which can be critical in aggressive disease requiring urgent treatment. However, the need for bridging therapy may lessen the importance of manufacturing speed, as treatment is administered while awaiting the return of the CAR T product.

Patient fitness and disease characteristics further inform therapy selection. For older or frail individuals, products with a lower risk of severe toxicity may be favored. Conversely, for patients with rapidly progressing disease, a faster-acting product may be prioritized. While there is no definitive evidence that one product is superior, some real-world data suggest slight differences in progression-free survival between options. Ultimately, the decision is individualized, factoring in disease urgency, patient comorbidities, expected toxicities, and logistical constraints to determine the most appropriate CAR T-cell therapy.