Abstract 1262: Gender bias in the association of pre-treatment cytokine signatures with response and survival in B cell lymphoma patients treated with anti-CD19 CAR T-cell therapy
Authors: Patel Manishkumar S. , Jalota Akansha , Mian Agrima , Bazeley Peter , Hunter Sara A. , Hill Brian T. , Gupta Neetu 
Published: June 2022

Abstract
Introduction: Despite the exceptional promise of anti-CD19 CAR T-cell therapy, 40-60% of relapsed or refractory large B-cell lymphoma (R/R LBCL) patients exhibit poor response and survival. Therefore, identification of pre-treatment markers of response to anti-CD19 CAR T-cell therapy is essential. Immune responses to infections and many autoimmune diseases exhibit gender bias, but it is not known if gender influences response to CAR T-cell therapy. We performed serum profiling to identify pre-treatment cytokines and chemokines associated with response and survival in male and female LBCL patients treated with axicabtagene ciloleucel (axi-cel).
Methods: Serum samples were collected from peripheral blood at the time of leukapheresis from 42 R/R LBCL patients treated with axi-cel. Multiplexed bead arrays were used to quantify baseline levels of 51 serum cytokines, chemokines and cytotoxic proteins. Unpaired Wilcoxon test was used to analyze the association of baseline cytokine levels with 3-month response, and Kaplan-Meier survival analysis for association with survival outcomes. Statistical analyses were performed using R and p&lt;0.05 was considered significant.
Results: The median age of patients was 61 y, and 62% of the patients were male. All patients had been previously treated with R-CHOP or R-EPOCH, and had a median of 3 prior lines of therapy, including 47.6% with autologous stem cell transplantation. Male non-responders (stable/progressive disease) had significantly higher baseline levels of IL-6, IL-8, IL-1RA, MIP-1α, GM-CSF and CRP compared to responders (complete/partial response). Higher levels of IL-6, IL-8, IL-27, and CRP were significantly associated with poor overall survival (OS), and IL-6, IL-8, MIP-1β, and CRP with poor progression-free survival (PFS) in male patients. Baseline metabolic tumor volume (MTV) and lactate dehydrogenase (LDH) levels were also significantly higher in male patients with poor OS and PFS. Finally, baseline IL-8 and CRP were significantly associated with baseline MTV and LDH levels in male patients.
Conclusions: Our data show that pre-treatment proinflammatory proteins IL-8, IL-6, CRP are associated with poor response and survival in axi-cel-treated male but not female LBCL patients. The correlation of high levels of these factors with high pretreatment tumor burden in male non-responder R/R LBCL patients is suggestive of an immunosuppressive tumor microenvironment that is unlikely to support optimal expansion of anti-CD19 CAR T cells, resulting in poor response and survival outcomes.
Citation Format: Manishkumar S. Patel, Akansha Jalota, Agrima Mian, Peter Bazeley, Sara A. Hunter, Brian T. Hill, Neetu Gupta. Gender bias in the association of pre-treatment cytokine signatures with response and survival in B cell lymphoma patients treated with anti-CD19 CAR T-cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1262.