Real-World Clinical Practice Insights from the TRANSCEND CLL004 Trial

CAR-T Cell Therapy in CLL Management

Lisocabtagene maraleucel (liso-cel) received FDA approval based on the TRANSCEND CLL 004 trial, which studied patients with at least two prior therapies including both covalent BTK and BCL-2 inhibitors. The trial demonstrated overall response rates around 40% with 22% complete responses and notable rates of undetectable minimal residual disease. CAR-T therapy selection requires careful consideration of patient age, fitness level, and disease characteristics. While CLL predominantly affects older patients, younger patients with high-risk features who have exhausted targeted therapies represent ideal candidates due to the potential for durable complete remissions extending beyond ten years in some cases. Recent data suggest that BTK inhibitor bridging therapy may improve CAR-T cell outcomes, with ibrutinib showing particular promise in enhancing T-cell function and CAR-T efficacy. Patient selection factors including disease bulk (lymph nodes under 5 cm associated with better responses) and timing of CAR-T referral relative to disease control are important considerations for optimizing outcomes.