Study on the Prognostic Value of Aberrant Antigen in Patients With Acute B Lymphocytic Leukemia

Chimeric antigen receptors redirected T cell (CAR-T cell) therapy is an effective means of treating relapsed/refractory acute B-lymphocytic leukemia, and new targets are needed to solve the recurrence after CAR-T cell treatment. A retrospective analysis of 194 patients with acute B-lymphocytic leukemia showed a poor prognosis for CD123 expression. To improve efficacy, CAR19 can be considered to bind to aberrant antigens such as CD123 to form a bispecific or multispecific antigen in CAR-T cell construction. Background: Approximately 30% to 60% of patients with acute B-lymphocytic leukemia (B-ALL) show as refractory or relapsed, which is one of the major causes of death in patients with B-ALL, but the methods of the treatment for relapsed/refractory B-ALL (R/R B-ALL) are limited. The chimeric antigen receptors redirected T cells (CAR-T cells) have showed a strong anti-leukemia role for B-ALL. About 90% of patients with R/R B-ALL treated with CD19-CAR-T cells achieved complete remission. However, 60% to 70% of patients relapsed after CAR-T cells treatment, which may be related to target antigen reduction or escape. New products are urgently needed to prevent and treat antigenic escapes causing recurrence. Patients and Methods: In this article, we retrospectively analyzed the immunophenotype of patients with B-ALL initially diagnosed in our center from January 2010 to December 2015 to determine whether aberrant antigen expression was associated with the prognosis of patients in order to find new targets for immunotherapy. Results: The results show that disease-free and overall survival in patients without aberrant antigen expression were better than patients with aberrant antigen expression. The most common abnormal antigens were CD123, CD13, and CD56. Correlation analysis showed a negative correlation between aberrant CD123 expression and both disease-free and overall survival. Conclusion: Therefore, in the construction of CAR-T cells in patients with R/R B-ALL, conventional CD19 can be combined with aberrant antigens such as CD123 to form CARs with bi-specific antigens or multi-specific antigens may achieve the purpose of improving efficacy. However, more clinical trials are needed.