TY - JOUR
T1 - CT-009 Prognostic Role of Lymphocyte to Monocyte Ratio in PTS Treated With CAR-T for Aggressive Lymphoma
AU - Bansal, Radhika
AU - Zhang, Henan
AU - Martinez, Kodi E.
AU - Hathcock, Matthew
AU - Shao, Zuoyi
AU - McCoy, Gabrielle Gonzalez
AU - Gonzalez-Guerrico, Anatilde
AU - Bennani, Nora
AU - Paludo, Jonas
AU - Wang, Yucai
AU - Johnston, Patrick B.
AU - Ansell, Stephen M.
AU - Kenderian, Saad
AU - Porrata, Luis
AU - Villasboas, Jose C.
AU - Lin, Yi
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - Background: Low absolute lymphocyte to monocyte ratio (ALC/AMC) predicts decreased survival in aggressive lymphoma (NHL) patients (pts) receiving chemotherapy and ASCT. We report the clinical significance of ALC/AMC and associated cellular phenotype changes in pts receiving chimeric antigen receptor T-cell (CART) 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 the clinical lab before lymphodepletion chemotherapy (LD). The 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. 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 group (>0.8, n=52), except for the use of prior ASCT and bridging therapy. The low ALC/AMC group also had higher CRP on the day of CAR-T infusion and was associated with shorter EFS and OS (EFS: 2.6 vs. 6.4 months, P<0.0001; OS: 5.3 months vs. not reached, P=0.0006), respectively. The prognostic association remained statistically significant on multivariate analysis that included prior ASCT, bridging therapy, and CRP. Compared to the high ALC/AMC group, the low ALC/AMC group had decreased CD4 Tem and increased CD16+CCR2+ monocytes (n=26). In addition, when comparing patients 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 biological 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.
AB - Background: Low absolute lymphocyte to monocyte ratio (ALC/AMC) predicts decreased survival in aggressive lymphoma (NHL) patients (pts) receiving chemotherapy and ASCT. We report the clinical significance of ALC/AMC and associated cellular phenotype changes in pts receiving chimeric antigen receptor T-cell (CART) 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 the clinical lab before lymphodepletion chemotherapy (LD). The 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. 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 group (>0.8, n=52), except for the use of prior ASCT and bridging therapy. The low ALC/AMC group also had higher CRP on the day of CAR-T infusion and was associated with shorter EFS and OS (EFS: 2.6 vs. 6.4 months, P<0.0001; OS: 5.3 months vs. not reached, P=0.0006), respectively. The prognostic association remained statistically significant on multivariate analysis that included prior ASCT, bridging therapy, and CRP. Compared to the high ALC/AMC group, the low ALC/AMC group had decreased CD4 Tem and increased CD16+CCR2+ monocytes (n=26). In addition, when comparing patients 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 biological 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.
KW - CAR-T
KW - CT
KW - Lymphoma
KW - biomarker
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U2 - 10.1016/S2152-2650(22)01637-8
DO - 10.1016/S2152-2650(22)01637-8
M3 - Article
C2 - 36164189
AN - SCOPUS:85138152627
SN - 2152-2650
VL - 22
SP - S430
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -