Challenges of minimal residual disease monitoring in patients with leukemia during chimeric antigen receptor modified T cell immunotherapy

Chimeric antigen receptor modified T cell (CAR-T) immunotherapy has achieved remarkable success in the treatment of hematological malignancies, especially for relapsed/refractory acute B lymphocytic leukemia (B-ALL) leukemia patients, most of whom could obtain complete remissions or partial remissions. However, clinical studies also found a as high as 50% total recurrence rate of these patients, in which more than 20% patients relapsed with tumor cells not expressing the primary CAR-T-targeted CD molecules. Increased relapses with negative targeted-molecules or even lost primary abnormal tumor gene, suggesting that immune escape and even clonal evolution events increased rapidly under the high-precision CAR-T immunotherapy pressure. Monitoring of minimal residual disease (MRD) is important to assess the efficacy and find recurrence trends early in a timely manner to guide further clinical intervention. The new features of disease recurrence after CAR-T treatment have put forward higher requirements for traditional and emerging MRD detection methods so as to ensure their effectiveness in the CAR-T treatment era.(Chin J Lab Med, 2018, 41: 175-179) Key words: Chimeric antigen receptor modified T cell; Leukemia; Minimal residual disease