Abstract IA13: Engineered T cells for cancer therapy

Abstract

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a limited survival. Chimeric antigen receptor (CAR)-modified T cells targeting CD19 may overcome the limitation of low complete response rates with conventional therapies with the potential to induce sustained remissions in patients with refractory B-cell malignancies. We previously reported preliminary results on three patients with refractory CLL. Here we report the mature results from our initial trial using CAR modified T cells to treat 14 patients with relapsed and refractory CLL (1). Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14–11 ×108 CTL019 cells (median 1.6 x 108 cells). Patients were monitored for toxicity, response, expansion and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8/14 (57%), with 4 complete remissions (CR), and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and CAR T cells have persisted and remain functional beyond 4 years in the first two patients achieving CR; no patient in CR has relapsed. All responding patients have developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease is not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL.

In separate studies we have asked whether the same CD19 CAR may have activity in tumors that do not express CD19. A patient with refractory multiple myeloma was treated with CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, following myeloablative chemotherapy (melphalan 140 mg/m2) and autologous stem cell transplantation (2). Four years earlier, autologous transplantation with a higher melphalan dose (200 mg/m2) had induced only a partial, transient response. Autologous transplantation followed by CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at last evaluation, 12 months after treatment. This response was achieved despite absence of CD19 expression in 99.95% of this patient's neoplastic plasma cells.

References:

1. Porter DL, et al. Science Transl Med, 2015 (in press)

2. Garfall A, et al. N Engl J Med, 2015 (in press)

Citation Format: Carl June. Engineered T cells for cancer therapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA13.