Abstract
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
Highlights
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL)
To explore the relevant factors affecting the efficacy, we routinely analyzed whether the complete remission (CR), overall survival (OS), and relapse-free survival (RFS) were related to patient’s baseline characteristics such as gender, age, number of cycles of chemotherapy, relapse, previous alloHSCT, and proportion of bone marrow (BM) blast cells; all results did not show significant differences (Table 2; Figs. 2b and 3b)
The CR/CR with incomplete hematologic recovery (CRi) rate in patients with extramedullary diseases (EMDs) other than central nervous system (CNS) was the lowest (28.6%); no significant difference existed between patients with CNS involvement only and the patients without EMDs (83.3% vs. 91.2%, p = 0.493) (Table 2)
Summary
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS These patient characteristics may hinder the efficacy of CAR T therapy. Patients with extramedullary diseases (EMDs) other than the central nervous system (CNS) involvement have the lowest remission rate (28.6%) comparing with patients with isolated CNS involvement and those without EMDs. The OS and RFS in patients with any subtype of EMDs, higher regulatory T cells (Tregs), or high-risk genetic factors are lower. Multivariable analyses reveal that EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS, so these patient factors may preclude the efficacy of CAR T therapy in r/r B-ALL. On the 180th day, over 10% blasts were detected in blood and BM
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