Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1-2 trial

Abstract

Increasing the remission rate and reducing the recurrence rate can improve the clinical efficacy of chimeric antigen receptor (CAR) T cell therapy in recurrent/refractory non-Hodgkin lymphoma (r/rNHL). In this open-label, single-arm phase I/II trial, 87 patients with r/rNHL, including 58 patients with aggressive diffuse large B-cell lymphoma and 24 with high tumour burden, received an infusion at doses of 0.5 × 10⁶-8 × 10⁶ TanCAR7 T cells per kilogram of body weight after conditioning chemotherapy. The best overall response rate was 78% (95% confidence interval [CI], 68-86); response rates were consistent across prognostic subgroups. The median follow-up was 27.7 months. The median progression-free survival was 27.6 months (95% CI, 11 to not reached). Cytokine release syndrome (CRS) occurred in 61 patients (70%) with 60% of cases being grade 1 or 2 and 10% being grade 3 or greater. Grade 3 CAR T cell-related encephalopathy syndrome (CRES) occurred in 2 patients (2%). Two patients died from treatment-associated severe pulmonary infection, and one died from CRS-related pulmonary injury between 1 and 3 months post infusion. Long-term remissions were observed following the use of TanCAR7 T cells in r/rNHL with a safety profile that included CRS but few cases of CRES.

Fig. 1. CONSORT flow diagram.

Among the 7 patients who were excluded from the study during screening, 2 failed in preculture, 1 had negative expression of both CD19 and CD20 by immunohistochemistry, and 4 had disease progression while waiting for hospitalisation. Among the 92 enroled patients, one patient failed leukapheresis, and another had AEs after leukapheresis. Before infusion, 1 patient had serious AEs, and 2 could not tolerate pretreatment due to disease progression. AEs adverse events.

Fig. 2. Best overall response rate based on subgroup.

ASCT autologous stem cell transplantation, CAR chimeric antigen receptor, CI confidence interval, DLBCL diffuse large B-cell lymphoma, ECOG Eastern Cooperative Oncology Group, FL follicular lymphoma, PMBCL primary mediastinal B-cell lymphoma, SPD sum of the product of the diameters, tFL transformed follicular lymphoma.

Fig. 3. Kaplan–Meier estimates of the duration of response, progression-free survival, and overall survival.

A Shows the duration of response of the 66 patients who had a response, including the patients with aggressive disease (including DLBCL, tFL and PMBCL) or FL. B Shows progression-free survival for all 87 patients who received an infusion, including the patients with aggressive disease (including DLBCL, tFL and PMBCL) or FL. The progression-free survival time was recorded as the date of TanCAR7 T cell infusion to the date of disease progression or death from any cause. Subjects not meeting the criteria for progression by the data analysis cut-off date were censored at their last evaluable disease assessment date. Data from 4 other patients were censored: 3 received interventional treatment, and 1 was lost to follow-up. C Shows the overall survival for all 87 patients who received an infusion or patients with aggressive disease (including DLBCL, tFL and PMBCL) or FL. The overall survival time was recorded as the date of TanCAR7 T cell infusion to the date of death from any cause. Patients who did not have an event had their data censored for the analyses at the date at which they were last known to be alive. DLBCL diffuse large B-cell lymphoma, FL follicular lymphoma, PMBCL primary mediastinal B-cell lymphoma, tFL transformed follicular lymphoma.