Real-World Studies Highlight CAR T-Cell Therapy Benefits and Chemotherapy Limits in Large B-Cell Lymphoma

Multiple real-world studies underscore the clinical value of CAR T-cell therapy in large B-cell lymphoma, showing that an early complete response predicts sustained remission while historical chemotherapy regimens yield poor outcomes in high-risk patients. Research published in Transplantation and Cellular Therapy analyzed data from 394 patients with LBCL who received CD19-targeting CAR T-cell therapy with axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel. The study found that reaching a complete response at an early time point was predictive of improved progression-free survival, with a hazard ratio for progression of 0.56 (P=.002) compared with partial response. Elevated levels of lactate dehydrogenase prior to lymphodepletion predicted worse progression-free survival (HR 2.67; P<.001) and inferior overall survival.

Response rates varied by product: for axicabtagene ciloleucel, the overall response rate was 81% by day 28 with a complete response rate of 49%; for tisagenlecleucel, the ORR was 62% with a CR rate of 48%; and for lisocabtagene maraleucel, the ORR was 89% with a CR rate of 55%. The median follow-up periods were 23 months for axicabtagene ciloleucel, 34 months for tisagenlecleucel, and 16 months for lisocabtagene maraleucel. The study authors noted that findings were not consistent across the evaluated drugs, indicating that more research is needed to determine which markers are predictive of relapse.

A separate single-center Austrian analysis published in Technology in Cancer Research and Treatment examined 278 patients with diffuse large B-cell lymphoma diagnosed between 2010 and 2018. Standard chemotherapy-based approaches produced acceptable outcomes in lower-risk patients but consistently poor results in high-risk disease and after frontline failure. The median progression-free survival for all treated patients was 8.2 years, and median overall survival was 11.1 years. Patients older than 80 years had a 3.53-fold higher risk of progression and a 7.09-fold higher risk of death compared with those younger than 61 years. High-risk International Prognostic Index groups had a median PFS of approximately 1 to 2 years, in contrast to not-reached medians in low-risk disease.

Second-line outcomes were particularly poor: only 59 patients (21.2%) received any second-line therapy, with a 2-year overall survival rate of 48.1% and a 5-year OS rate of 37.4%. Patients theoretically eligible for CAR T-cell therapy represented a subgroup with especially dismal historical outcomes. In these patients, median OS from frontline therapy was less than 1 year, with a 2-year OS rate of 26.6% and a 5-year OS rate of 20.7%. Median PFS-2 was only 0.19 years, highlighting the profound unmet need in this population.

Additional real-world registry data from the French DESCAR-T registry and REALYSA cohort, discussed in recent perspectives, evaluated second-line axicabtagene ciloleucel versus standard-of-care salvage therapy in early relapsed/refractory DLBCL. The comparison highlighted an event-free survival advantage with CAR T-cell therapy, with a 1-year EFS of 46% versus 16% in the standard-of-care arm. These real-world data inform routine second-line treatment decision-making and underscore the importance of timely referral for eligible patients.

Collectively, these findings can guide clinicians in counseling patients about evolving risk over time, refining surveillance intensity, and considering timely salvage or consolidation strategies. They also provide an outcome benchmark for patient populations now receiving CAR T-cell therapy as a novel standard of care.