CD19嵌合抗原受体T细胞治疗病灶大于7.5 cm的复发/难治B细胞淋巴瘤肿瘤局部反应与疗效分析

OBJECTIVE: To observe the local reactions and efficacy of CD19 CAR-T therapy in recurrence/refractory B-cell non-Hodgkin's lymphoma (R/R NHL) patients with >7.5 cm lesions. METHODS: 32 R/R NHL patients with >7.5 cm lesions were enrolled and injected with CD19 CAR-T cells. Flow cytometry was used to detect and observe the amplification of CD19 CAR-T cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines in peripheral blood of patients. The side effects of CD19 CAR-T cell therapy included systemic side effects and local reactions of tumor. The local side effects were observed by Ultrasound, Computed tomography and Magnetic resonance imaging. Treatment options included glucocorticoid, interleukin-6 antibody and drainage of exudate. Overall response rate (ORR) and overall survival rate (OS) were observed. RESULTS: ①Among the 32 patients, CR (40.63％), PR (31.25％) and ORR (71.88％) were 13, 10 and 23, respectively. ②In all 23 patients received ORR, 13 patients had grade 1–2 CRS, while 10 patients had grade 3–4 CRS. All the 9 patients in the SD+PD group had grade 1–2 CRS（P＝0.030）. ③A total of 15 patients with tumor local reactions, included 9 patients with CR, 5 patients with PR and 1 patient with SD. The local reactions of the tumor included that the diameter of the superficial lesions increased with redness, swelling and heat pain. The deep lesions presented abdominal pain, abdominal distension, suffocation and local pain，and burning of the tumor. The deep lesions were enlarged or accompanied by local edema. The local exudative lesions were found in the abdominal cavity and pleural cavity. ④ Peak proportion of CD19 CAR-T cells in ORR group was higher than that of in SD+PD group［16.8％（5.3％–48.2％）vs 2.9％（1.5％–5.7％）, z＝−4.297, P<0.001］. The peak proportion of CD19 CAR-T cells in ORR group with local reactions was higher than that of in patients without local reactions［22.2％（10.5％–48.2％）vs 12.6％（5.3％–21.6％）, z＝−3.213, P＝0.001］. The peak proportion of CD19 CAR-T cells in multiple lesion group was higher than that of in single lesion group［35.8％（1.5％–48.2％）vs 16.8％（10.5％–18.5％）, z＝−2.023, P＝0.040］. ⑤Occurrence of local reactions and tumor shrinkage time were both delayed compared with systemic side effects. ⑥In the ORR group, the OS of patients with tumor local reactions was longer than that of patients without tumor local reactions, but there was no difference in the two groups（75％ vs 34.6％, P＝0.169）. CONCLUSION: CD19 CAR-T cell therapy in R/R NHL patients with >7.5 cm lesions might cause tumor local reactions later than systemic side effects. Clinicaltrial: ChiCTR1800018059