AUTHOR=Xu Qianwen , Xue Lei , An Furun , Xu Hui , Wang Li , Geng Liangquan , Zhang Xuhan , Song Kaidi , Yao Wen , Wan Xiang , Tong Juan , Liu Huilan , Liu Xin , Zhu Xiaoyu , Zhai Zhimin , Sun Zimin , Wang Xingbing 

TITLE=Impact of Consolidative Unrelated Cord Blood Transplantation on Clinical Outcomes of Patients With Relapsed/Refractory Acute B Lymphoblastic Leukemia Entering Remission Following CD19 Chimeric Antigen Receptor T Cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.879030

DOI=10.3389/fimmu.2022.879030

ISSN=1664-3224

ABSTRACT=Background: While chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, its high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve prognosis of patients who entering remission after CAR-T therapy with different characteristics through subgroup analysis.
Methods: We reviewed 53 patients with relapsed/refractory (R/R) acute B lymphoblastic leukemia (B-ALL) successfully infused with CD19 CAR-T cells and achieved complete remission (CR). 25 patients received consolidative UCBT (UCBT group) and 28 patients did not accept any intervention until relapse (non-UCBT group). Subgroup analysis on prognosis was then performed according to gender, age, number of previous relapses, tumor burden, presence of poor prognostic markers and structure of CAR.
Results: Compared with the non-UCBT group, patients who underwent consolidative UCBT had better median event-free survival (EFS; 12.3 months versus 6.2 months; P=0.035) and relapse-free survival (RFS; 22.3 months versus 7.2 months; P=0.046), while no significant difference was found in overall survival (OS; 30.8 months versus 15.3 months; P=0.118). Subsequent multivariate analysis revealed that bridging to UCBT was a protective factor for RFS (P=0.048) but had no significant effect on EFS (P=0.205) or OS (P=0.541). In subgroup analysis, UCBT has an added benefit in patients with specific characteristics. Patients who experienced ≥ 2 relapses or with sustained non-remission (NR) showed a better RFS (P=0.025) after UCBT. Better EFS was seen in patients with poor prognostic markers (P=0.027). In subgroup with pre-infusion minimal residual disease (MRD) ≥ 5% or with extramedullary disease (EMD), UCBT significantly prolonged EFS (P=0.009), RFS (P=0.017), and OS (P=0.026). Patients with occurrence of aGVHD appeared to have a longer duration of remission (P=0.007).
Conclusion: Consolidative UCBT can to some extent improve clinical outcomes of patients with R/R B-ALL entering remission following CD19 CAR-T therapy, especially in patients with more recurrences before treatment, patients with poor prognostic markers, and patients with higher tumor burden. The occurrence of aGVHD after UCBT was associated with better RFS.