Abstract 837P
Background
Anbalcabtagene autoleucel is a novel anti-CD-19 CAR-T therapy that has shown promising clinical results, with a complete response (CR) rate of 73.7% in relapsed or refractory LBCL patients at interim analysis. This biomarker analysis aims to understand the mechanism associated with the treatment outcome.
Methods
Patients with relapsed or refractory LBCL were enrolled to receive Anbal-cel at a dose of 2x106 cells/kg. Tumor biopsies were performed at baseline to assess the expression levels of CD19, PD-L1, and CD112/CD155. Peripheral blood mononuclear cell (PBMC) samples for immune phenotyping and serum sampled for ctDNA analysis were collected at day 0, 14, 28, and 3-month intervals thereafter until progression.
Results
PD-1 and TIGIT were highly expressed on baseline PBMC. PD-1 was expressed more on CD8+ CAR+ T-cells whereas TIGIT on CD4+ CAR+ T-cells. PD-1, LAG-3 and TIM-3 expressions were significantly increased from D14 at non-CR group. TIGIT expression was significantly increased at D28 at non-CR group. The non-CR group demonstrated the significantly increased level of IL-4+/ IL-5+ Th2 type CAR+ T-cells whereas GATA+ Th2/Tc2 type CAR+ T-cells were significantly lower in non-CR group. Additionally, CD57+CD27-CAR+ T-cells, a marker of terminal differentiation/ functional senescence, were significantly increased in the non-CR group from D14. CD226+ CAR+ T-cells were also significantly lower in the non-CR group. CD45RA+ CAR+ TEFF/EMRA cells post-infusion were significantly lower in the non-CR group and CD38+HLA-DR+ CAR+ T-cells, a marker of susceptibility of cell death, were significantly higher in the non-CR group. The activation of CAR+ T-cells measured by ICOS, 4-1BB, CD226 and CD94 was not different between the two groups. The most frequently detected mutations were related to cell cycling, epigenetic regulation, immune escape, apoptosis etc. Changes in ctDNA concentration were reversely correlated with treatment outcome.
Conclusions
Anbal-cel’s unique immunologic and genetic changes demonstrated potential to correlate with treatment outcomes and warrant to confirm with more data.
Clinical trial identification
CRC01-01 (NCT04836507).
Editorial acknowledgement
Legal entity responsible for the study
Curocell Inc.
Funding
Curocell Inc.
Disclosure
Y. Koh: Financial Interests, Institutional, Advisory Board: Curocell. J.R. Kim: Financial Interests, Personal, Member: Curocell. All other authors have declared no conflicts of interest.
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