Auto-HCT outperforms CAR-T therapy in patients with large B-Cell lymphoma achieving complete remission after chemotherapy

Patients with large B-cell lymphoma (LBCL) may receive bridging chemotherapy before receiving CAR-T therapy, with a small fraction achieving a partial or complete response (PR or CR). A previous study demonstrated superior outcomes when patients achieving PR received haematopoietic cell transplantation (HCT) instead of CAR-T. In line with these results, this retrospective real-world analysis showed that, for LBCL patients in CR, auto-HCT is associated with lower relapse rates and improved progression-free survival compared to CAR-T, supporting the use of auto-HCT in this patient population.

CAR-T therapy is the second-line standard of care (SOC) therapy for patients with relapsed large B-cell lymphoma (LBCL) based on the results of the head-to-head trials ZUMA-7 and TRANSFORM. These trials showed superior efficacy of CAR-T therapy compared to the SOC salvage chemotherapy followed by auto-haematopoietic cell transplantation (HCT). However, in practice, access to CAR-T is sometimes delayed due to logistical issues, and patients may receive interim (bridging) chemotherapy, with a small fraction achieving a partial or complete response (PR or CR). Having chemosensitive disease, these patients can also be considered for auto-haematopoietic cell transplantation (HCT). Importantly, the superior efficacy of auto-HCT over CAR-T in DLBCL has been demonstrated in patients achieving PR.

This raises a critical question: for patients achieving CR, which treatment modality is more appropriate: auto-HCT or CAR-T? To address this question, this study used data from the Centre for International Blood and Marrow Transplant Research (CIBMTR) to compare outcomes between DLBCL patients in CR who received either auto-HCT or CAR-T therapy.

Methods

This retrospective real-world analysis used data from the CIBMTR registry and included patients with diffuse LBCL or primary mediastinal lymphoma, aged 18-75 years, who achieved CR after receiving salvage chemotherapy. These patients subsequently received CAR-T or auto-HCT while in a CR. The primary endpoints included progression-free survival (PFS) and overall survival (OS). Treatment-related mortality (TRM) and relapse rate were among the secondary endpoints.

Results

This retrospective analysis included 360 patients with LBCL who achieved CR before receiving either CAR-T (n=79) or auto-HCT (n=281). Among those who received CAR-T, 42 received tisagenlecleucel (53.2%), 36 axicabtagene ciloleucel (45.6%) and one lisocabtagene maraleucel (1.3%). The median follow-up was 24.7 months for the CAR-T cohort and 49.7 months for the auto-HCT cohort.

In an univariate analysis, treatment with CAR-T was associated with a higher rate of relapse at two years (48% vs. 27.8% in the auto-HCT arm; p < 0.001), and lower PFS (47.8% vs. 66.2%; p < 0.001) and OS (65.6% vs. 78.9%; p=0.037) rates. There was no difference in the 2-year TRM rates between the arms (4.1% vs. 5.9%; p=0.673). In patients with early relapse (within the first 12 months), treatment with CAR-T was associated with a higher relapse rate (46.3% vs. 25%; p<0.001) and an inferior PFS rate (48.4% vs. 68.2%; p=0.001). However, in contrast to the overall cohort, no significant OS differences were observed between the CAR-T and auto-HCT arms (66.3% vs. 79.6%, respectively; p=0.131). In the multivariable analysis of outcomes, treatment with CAR-T was associated with a higher risk of relapse (HR[95%CI]: 2.18[1.48-3.20]; p <0.0001) and an inferior PFS (HR[95%CI]: 1.83[1.27-2.63]; p=0.0011) compared to auto-HCT. There was no difference in the risk of TRM (HR[95%CI]: 0.59[0.19-1.83]; p=0.3632) or OS (HR[95%CI]: 1.44[0.91-2.28]; p=0.123).

The most common cause of death in both cohorts remained lymphoma (68% vs. 60% in the CAR-T and auto-HCT arms, respectively), followed by infections (12% vs. 16.5%). Additionally, second malignancies (3.5%) and cardiac failure (3.5%) were observed in the auto-HCT cohort, and pulmonary failure (8%) in the CAR-T cohort.

Conclusions

In conclusion, for patients with relapsed LBCL achieving CR, treatment with auto-HCT was associated with a lower relapse rate and improved PFS compared to CAR-T, even in cases of early treatment failure (within 12 months). These findings align with previously reported improved clinical outcomes with auto-HCT compared to CAR-T in patients achieving PR. These data support the use of auto-HCT in patients with relapsed LBCL achieving a CR.

Reference

Shadman M, Wooahn K, Kaur M, et al. Autologous Transplant (auto-HCT) Is Associated with Improved Clinical Outcomes Compared to CAR-T Therapy in Patients (pts) with Large B-Cell Lymphoma (LBCL) Achieving a Complete Remission. Presented at ASH 2023; Abstract 781.