Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma

Abstract

Chimeric antigen receptor (CAR) T cells are emerging as a novel treatment for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (B-NHL), and combination with PD1 inhibitors may further improve the efficacy of anti-CD19 CAR (CD19 CAR)-T cells in the treatment of lymphomas. In a single-center study, we evaluated the safety and efficacy of a combination therapy with CD19 CAR-T cells and an anti-PD-1 antibody (nivolumab) in patients with relapsed/refractory B-NHL. A total of 11 patients with refractory/relapsed B-NHL were recruited and subsequently received CD19 CAR-T cells and nivolumab. The primary end points were safety and feasibility. The infusions were safe, and no dose-limiting toxicities occurred. Grade 1 or 2 cytokine release syndrome (CRS) was observed in 25% (3/11) and 50% (6/11) of the patients, respectively, and only one patient (1/11) experienced neurotoxicity. The objective response rate (ORR) and complete response (CR) rate were 81.81% (9/11) and 45.45% (5/11), respectively. The median follow-up time was 6 (1~15) months. The median progression-free survival (PFS) time was 6 months (1~14 months), and 3 patients continued to have a response at the time of this writing. Our study demonstrated that the combination of CD19 CAR-T cells and nivolumab was feasible and safe and mediated potent anti-lymphoma activity, which should be examined further in prospective clinical trials in refractory/relapsed B-NHL.

Keywords: B-cell non-Hodgkin lymphoma (B-NHL); anti-CD19 chimeric antigen receptor T cells; combination; immune check point blocade; safe and effective.

Figure 1

Clinical response and response duration in 11 enrolled patients.

Figure 2

(A) Whole-body scans showing lymphoma lesions in Patient 7 detected by PET/CT before and after CAR-T cell therapy. (B,C) The black line represents the previous CD19 CAR-T cell infusion, and the green line represents the later combination treatment. (D) Patient 8 had a bone marrow involvement. These malignant B-cell disappeared after CD19 CAR-T infusion.

Figure 3

(A) Peripheral blood CD19 CAR-T cells in patients receiving treatment. Patients who obtained a CR are represented in green, patients who obtained a PR are represented in blue, and patients who had no response are represented in red. (B) Patient 8 had a bone marrow involvement. These malignant B-cell disappeared after CD19CAR-T infusion. (C) Changes in inflammatory marker levels in patients after CD19 CAR-T cell and nivolumab infusion. The green lines, blue lines and red lines represent patients having obtained a CR, PR, or NR, respectively. A, IL-2R. B, IL-6. C, IL-8. D, IL-10. E, TNF-α. F, CRP. G, Ferritin.