CT-016 Prognostic Role of Lymphocyte-to-Monocyte Ratio in Patients Treated With CAR-T for Aggressive Lymphoma.

BACKGROUND: Low absolute lymphocyte-to-monocyte ratio (ALC/AMC) predicts decreased survival in aggressive lymphoma (NHL) patients (pts) receiving chemotherapy and autologous stem cell transplantation (ASCT). We report the clinical significance of ALC/AMC and associated cellular phenotype changes in pts receiving chimeric antigen receptor T-cell (CAR-T) therapy.

METHODS: We conducted a retrospective chart review of all pts who received axicabtagene ciloleucel for NHL at Mayo Clinic, Rochester, between 6/2016 and 12/2020. ALC and AMC were obtained from clinical labs before lymphodepletion chemotherapy (LD). A receiver operator curve was generated using nominal logistic regression on ALC/AMC to predict complete remission (CR). Survivals were calculated using the Kaplan-Meier method. Blood immune phenotypes were assayed by multiparametric flow cytometry.

RESULTS: Low ALC/AMC (≤0.8, n=29) prior to LD was associated with a lower CR rate (AUC=0.68, P=0.0004). Baseline characteristics were similar between the low and high ALC/AMC groups (>0.8, n=52), except for the use of prior ASCT and bridging therapy. The low ALC/AMC group also had higher C-reactive protein (CRP) on the day of CAR-T infusion and was associated with shorter event-free survival (EFS) and overall survival (OS) (EFS: 2.6 vs. 6.4 months, P<0.0001; OS: 5.3 months vs. not reached, P=0.0006). The prognostic association remained statistically significant in multivariate analysis that included prior ASCT, bridging therapy, and CRP. Compared with the high ALC/AMC group, the low ALC/AMC group had decreased CD4 effector memory T cells and increased CD16+ CCR2+ monocytes (n=26). In addition, when comparing pts who achieved CR initially and relapsed versus those who maintained durable CR for 6 months or longer, there was a difference in these phenotypes as well as the number of CD27+ CD45RA+ CD62L+ CD8 T cells and PD-1+TIGIT+ T cells.

CONCLUSIONS: ALC/AMC is a clinically accessible test that is strongly associated with CAR-T response and survival. Immune characterization revealed that the biologic effect is not just associated with cell numbers. Phenotypes, such as monocytes with inflammatory capacity and T-cell subsets, may further distinguish between primary refractory disease, early relapse, and durable response. These data could inform future therapeutic strategies to improve clinical outcomes with CAR-T.