ASCT vs CART for patients with relapsed LBCL in PR: role of TMTV

Autologous stem cell transplant (ASCT) is currently the standard consolidative approach for fit patients with large B-cell lymphoma (LBCL) who achieve a complete response (CR) after salvage therapy, whereas autologous anti-CD19 chimeric antigen receptor T-cell therapy (CART) is commonly reserved for those who are chemo-refractory or ASCT-ineligible.^1-6 However, the optimal management for patients who achieve a partial response (PR) remains debated. In a recently published retrospective registry study, 222 patients with LBCL who received ASCT in PR were compared with 126 patients in PR who received CART, with a significantly lower relapse/progression rate observed in the former.⁷ However, in addition to including patients who were not restaged after bridging therapy, the study did not account for differences in baseline tumor burden before ASCT or CART, because the total metabolic tumor volume (TMTV) may significantly vary among patients with PR, and prior studies have revealed that high TMTVs can negatively affect the patient’s response to CART.⁸ This is a single-center retrospective study of all patients with relapsed and/or refractory LBCL who achieved a PR based on the Lugano 2014 classification and then underwent either ASCT between 2010 and 2021 or CART with axicabtagene ciloleucel between 2018 and 2022.⁹ Patients who previously received ≥2 lines of systemic therapy were included in the study. Refractory disease was defined as a lack of response to any prior line of systemic therapy before the latest documented PR. Patients without restaging positron emission tomography scans after bridging therapy were excluded; patients who had previously received CART (for the ASCT cohort) or ASCT (for the CART cohort) were also excluded. The study was approved by The University of Texas MD Anderson Cancer Center institutional review board and was conducted in accordance with the institutional guidelines and principles of the Declaration of Helsinki. The clinical characteristics and laboratory features were collected before the initiation of conditioning and lymphodepleting chemotherapy. TMTV was calculated as previously described.⁸ The primary end point was a 24-month relapse/progression rate, defined as the time from infusion to relapse or disease progression. The secondary end points included overall survival and the identification of factors associated with TMTV. Survival curves were calculated using Kaplan-Meier estimates, and the cumulative incidence function with Gray test for subdistribution hazards was used to compare the relapse/progression rates in the 2 cohorts to account for competing events. The Fine-Gray model was used for multivariate analysis of factors significantly associated with the relapse/progression rate on univariate analysis. The median follow-up for all patients was calculated using the inverse Kaplan-Meier method. For the whole population, the difference in TMTV, measured as a continuous variable, between patient groups was evaluated using the Mann-Whitney test. To adjust for differences in baseline characteristics, propensity score matching analysis was used with a 1:1 ratio. P ≤ .05 (two-tailed) was considered statistically significant. Statistical analyses were performed using SAS 9.4, SPSS 24, and GraphPad Prism 8.