Lymphocyte dynamics after CAR-T therapy for non-Hodgkin lymphoma

Chimeric antigen receptor T cells directed against CD-19 are highly effective therapies for various subtypes of B-cell non-Hodgkin lymphoma (NHL). We have studied the impact of patient-specific lymphocyte growth kinetics after lymphoid depletion chemotherapy on both long-term outcomes and toxicity in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The growth of the lymphocyte populations early after chimeric antigen receptor T-cell (CAR-T) therapy is well described by an exponential function and the growth rate of the cells appears to be one of the most critical determinants of overall survival in these patients. The maximum lymphocyte peak and the area under curve for lymphocytes within the first 4 weeks after CAR-T therapy had no impact on survival. Receiver operator characteristic analysis determined that a replication rate ≥0.3876/day is associated with superior rates of complete response and durable responses. This threshold is associated with higher grades of cytokine release syndrome and the need for tocilizumab. However, patients with this threshold have a median overall survival of 3.04 years compared to 1.035 years for patients with slower lymphocyte replication (p = 0.0206). The major determinant of depth of response and durability of response to CAR-T in NHL is the speed of lymphocyte expansion.