Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia

CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9–24.9). Median follow-up after infusion was 7.1 months (0.5–42). BCA was observed 7 days after infusion (3–8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41–99) and 13% undetectable IgA levels at 185 days (11–308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.