Anti-CD19 CAR-T cell therapy in relapsed/refractory t(8;21) acute myeloid leukemia with aberrant CD19 expression

Abstract

Background: T (8; 21) acute myeloid leukemia (AML) is a special type of acute leukemia, and exhibits a heterogeneous prognosis, with a long-term relapse rate of about 40%. Once t(8; 21) AML patients experience relapse, they have an extremely poor prognosis, with a 5-year overall survival rate of less than 15%. Therefore, it is crucial to develop effective strategies to improve the prognosis of relapsed/refractory (R/R) t(8; 21) AML. CD19 is a specific B-cell surface marker, but it is aberrantly expressed in 50-80 % of t(8; 21) AML patients. CAR-T cells targeting aberrant cell-surface antigens could induce the depletion of tumor cells without the destruction of hematopoiesis. Therefore, CD19 might be a promising target for CAR-T cell therapy in R/R t(8; 21) AML with aberrant CD19 expression. The present study is aimed to explore the efficacy and safety of CD19 CAR-T cell therapy in R/R t(8;21) AML with aberrant CD19 expression.

Methods: In the present study, 3 R/R t(8;21) AML patients with aberrant CD19 expression were enrolled. After lymphodepleting chemotherapy, 3 patients received autologous CAR-T cell infusion at a dose of 1.0 × 10^6 cells/kg, 2.0 × 10^6 cells/kg, and 2.0 × 10^6 cells/kg, respectively.

Results: They all achieved CD19 negativity approximately half a month after CD19 CAR-T cell infusion. These indicate CD19 CAR-T cell therapy is effective in R/R t(8;21) AML with aberrant CD19 expression. However, patient 1 and patient 2 rapidly relapsed within 3 months after CD19 CAR-T cell therapy. Subsequently, patient 1 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fortunately, patient 1 achieved mCR 2 months after allo-HSCT.

Conclusion: Considering the short-term remission of CD19 CAR-T cell therapy in R/R t(8;21) AML, allo-HSCT might be performed as soon as possible to consolidate the efficacy of CAR-T cell therapy and reduce the risk of relapse.

Keywords: CD19 CAR-T cell therapy; aberrant CD19 expression; hematological remission; molecular remission; t(8; 21) acute myeloid leukemia.

Figure 1

(A) The percentage of leukemic blasts in bone marrow after CAR-T cell infusion in patient 1. Red dots represent leukemic blasts and dark blue dots represent normal primitive hematopoietic cells, which are also applicable to patient 2 and patient 3. Purple dots represent B-progenitor cells. (B) The percentage of leukemic blasts in bone marrow after CAR-T cell infusion in patient 2. (C) The percentage of leukemic blasts in bone marrow after CAR-T cell infusion in patient 3. On day 16, no leukemic blasts were detected, as shown by the normal development and differentiation of primitive hematopoietic cells. On day 32, 0.13% of leukemic blasts were detected by FCM in bone marrow, which abnormally expressed several markers, such as CD38 dim, bright CD33, bright CD13, and bright HLA-DR. (D) The changes of CD19+ leukemic blasts in bone marrow after CAR-T cell infusion in 3 patients. (E) The transcript levels of RUNX1::RUNX1T1 in bone marrow after CAR-T cell infusion in 3 patients.

Figure 2

(A) The percentage of CD19 CAR-T cells in peripheral blood from 3 patients after CAR-T cell infusion. (B) The absolute number of CAR-T cells in peripheral blood from 3 patients after CAR-T cell infusion. (C) The changes of temperature in 3 patients after CAR-T cell infusion. (D) The levels of IL-6 in 3 patients after CAR-T cell infusion. (E) The levels of IL-8 in 3 patients after CAR-T cell infusion. (F) The levels of IL-10 in 3 patients after CAR-T cell infusion.