AUTHOR=Lyu Cuicui , Cui Rui , Wang Jia , Mou Nan , Jiang Yanyu , Li Wei , Deng Qi 

TITLE=Intensive Debulking Chemotherapy Improves the Short-Term and Long-Term Efficacy of Anti-CD19-CAR-T in Refractory/Relapsed DLBCL With High Tumor Bulk

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.706087

DOI=10.3389/fonc.2021.706087

ISSN=2234-943X

ABSTRACT=<p>Anti-CD19 chimeric antigen receptor T (CAR-T) therapy has achieved remarkable effects in refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). However, when high tumor bulk occurs, patients tend to early progression after CAR-T therapy. Here, we investigated whether pretreatment with intensive debulking chemotherapy could improve the outcome of CAR-T in such patients. Fifty-seven patients with R/R DLBCL were enrolled, and 42 patients received anti-CD19-CAR-T therapy, among which, 25 patients (the combined group) with high tumor bulk received debulking chemotherapy and anti-CD19-CAR-T therapy sequentially. Another 17 patients (the control group) without high tumor bulk received anti-CD19-CAR-T therapy only. According to the response to debulking chemotherapy, patients of the combined group were divided into chemo-sensitive and chemo-refractory groups. Within 2 months, the objective response rate (ORR) was higher in the chemo-sensitive group than in the chemo-refractory group (<italic>P</italic> = 0.031). Grades 1–3 cytokine release syndrome (CRS) was reported, and no difference was shown in CRS grade distribution between the chemo-sensitive and chemo-refractory groups (<italic>P</italic> = 0.514). The chemo-sensitive group demonstrated longer overall survival (OS) than the chemo-refractory group (<italic>P</italic> = 0.042). Of the chemo-sensitive group, the 1-year disease free survival (DFS) and OS rates were 52.6 and 57.9%, respectively. Besides, no significant differences were found in ORR, DFS, and OS between the chemo-sensitive and control groups (ORR: <italic>P</italic> = 0.593; DFS: <italic>P</italic> = 0.762; OS: <italic>P</italic> = 0.531). In summary, effective debulking chemotherapy improved the short-term ORR and long-term OS of CAR-T therapy in R/R DLBCL with high tumor bulk, with outcomes comparable to those of R/R DLBCL without high tumor bulk. The clinical trial of our study was registered at <uri xlink:href="http://www.chictr.org.cn/index.aspx" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chictr.org.cn/index.aspx</uri> as <italic>ChiCTR-ONN-16009862</italic> and <italic>ChiCTR1800019622</italic>.</p><sec><title>Clinical Trial Registration</title><p><uri xlink:href="http://www.chictr.org.cn/index.aspx" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chictr.org.cn/index.aspx</uri>, identifier (<italic>ChiCTR-ONN-16009862</italic> and <italic>ChiCTR1800019622)</italic>.</p></sec>