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Phase 1b Trial Shows Safety of CD19-7x19 CAR-T Cells in Combination With Anti-PD-1 Antibody for R/R DLBCL
Data of CD19-7x19 CAR-T cells plus anti-PD-1 antibody from a groundbreaking clinical trial were presented at the 2021 American Society of Hematology (ASH) Annual Meeting to highlight the safety and efficacy of this new strategy.
“Using a series of in-vitro studies, we demonstrated that IL-7 and CCL19 prominently promoted the cytotoxicity and the expansion of CAR-T cells. On the other hand, the existence of different immunosuppressive pathways such as PD-1/PD-L1 pathway can restrict the full potential of CAR-T therapy. Thus, it is reasonable to postulate that CD19-specific CAR-T cells that express both IL-7 and CCL19 (CD19-7×19 CAR-T cells) in combination with anti-PD-1 antibody may constitute a potential option for R/R DLBCL,” explained Wenbin Qian, MD, PhD, Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, and colleagues.
A total of 8 patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) were enrolled in the phase 1b, single-arm, open-label, single-center trial. Lymphoma biopsies were immunostained for targets including CD19 and PD-L1 expression was confirmed. CD19-7×19 CAR-T cells were administrated at dose of 1 to 3×106 CAR-T cells/kg following lymphodepleting chemotherapies using fludarabine (30 mg/m2) and cyclophosphamide (500 mg/m2).
The primary endpoints were safety and objective response rate (ORR).
“Among the 8 pts, 3 received infusion dose of 1 × 106/kg, 3 received the dose of 2 × 106/kg, and 2 received the dose of 3 × 106/kg. 2 patients (25%) developed > grade 2 cytokine release syndrome and 2 (25%) developed neurotoxicity (grade 3). These adverse effects resolved quickly after intervention,” detailed Dr Qian and colleagues.
Notably, among the 7 patients evaluated at 3 months follow-up, 4 had a complete response (CR), 1 partial response (PR), and 2 disease progression (PD). The overall response rate was 5/7 and CR rate was 4/7.
“These results showed the feasibility, controllable toxicities, and marked response rate with this potential approach for R/R DLBCL. However, it remains unclear whether long term remission rate can be achieved. Long term follow-up and additionally enrolled patients would be necessary,” concluded Dr Qian and colleagues.
Wenbin Q, Zhao A, Liu H, Lei W, Liang Y, and Yuan X. Safety and Efficacy of CD19 CAR-T Cells Co-Expressing IL-7 and CCL19 in Combination with Anti-PD-1 Antibody for Refractory/Relapsed DLBCL: Preliminary Data from the Phase 1b Trial (NCT04381741). Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3843.
