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

Radhika Bansal, Henan Zhang, Kodi Martinez, Matthew Hathcock, Zuoyi Shao, Gabrielle McCoy, Anatilde Gonzalez Guerrico, Nora Bennani, Jonas Paludo, Yucai Wang, Patrick Johnston, Stephen Ansell, Saad Kenderian, Luis Porrata, Jose Villasboas Bisneto, Yi Lin

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)S430
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • CAR-T
  • CT
  • biomarker
  • lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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