Abstract
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 (P = 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 (P = 0.514). The chemo-sensitive group demonstrated longer overall survival (OS) than the chemo-refractory group (P = 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: P = 0.593; DFS: P = 0.762; OS: P = 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 http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and ChiCTR1800019622.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier (ChiCTR-ONN-16009862 and ChiCTR1800019622).
Highlights
Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) has poor therapeutic response and prognosis
15 patients with high tumor bulk did not participate in anti-CD19-chimeric antigen receptor T (CAR-T) therapy after debulking chemotherapy due to personal preference
As previous correlative analyses have largely focused on the toxicity of CAR-T therapy, the factors associated with the durable response of such treatment remain incompletely elucidated
Summary
Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) has poor therapeutic response and prognosis. The standard treatment for R/R DLBCL involves high-dose chemotherapy followed by autologous stem cell transplantation [1]. The long-term remission rate associated with such treatment is only 10–20% [2, 3]. Anti-CD19 chimeric antigen receptor T (CAR-T) therapy has shown significant effects in B-cell malignancies. Data from the ZUMA-1 and JULIET studies have reported objective response rates (ORR) of 50–80% and complete response (CR) rates of 30– 50% in B-cell lymphomas [4, 5]. The NCCN guidelines (version 4.2019) have recommended CAR-T therapy for DLBCL patients achieving partial response (PR) following second-line therapy and for those with disease relapse after achieving CR to secondline therapy or progressive disease (PD)
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