Use of immune repertoire sequencing analysis to detect differences in treatment responses for advanced esophageal squamous cell carcinoma treated with camrelizumab and platinum-based chemotherapy.

Abstract

488 Background: The study evaluated the efficacy and safety of camrelizumab combined with platinum-based chemotherapy (platinum plus paclitaxel [TP] or fluorouracil [FP] agents) as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC), and explored potential biomarkers for treatment response using immune repertoire (IR) sequencing. Methods: In this multi-center, prospective cohort study, advanced ESCC patients were treated with camrelizumab and TP or FP chemotherapy. Primary outcome was 1-year progression free survival (PFS). Secondary outcomes included 1-year overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Patients were categorized based on their treatment responses into the non-ORR and ORR groups. IR sequencing was exploratorily performed on the peripheral blood mononuclear cells from 15 patients in each group. Results: From June 2020 to April 2023, 88 out of 98 screened patients were enrolled, with a median follow-up of 15.9 months. The 1-year PFS was 56.8%, OS was 68.2%, ORR was 64.8%, and DCR was 91.1%. Most treatment-related adverse events were grade 1-2, though 12.5% experienced grade ≥3 toxicities. The FP regimen's efficacy was comparable to the TP regimen. The analysis of the complementarity-determining region 3 polypeptide sequences revealed significant differences in amino acid composition between the non-ORR and ORR groups in T-cell receptor beta-chain (TRB) and immunoglobulin heavy chain (IGH) repertoire. Furthermore, the ORR group exhibited a more concentrated distribution of clones within TRB. Two V genes (TRBV29-1 and TRBV4-1) and one J gene (TRBJ1-3) in the TRB region, along with six V genes (IGHV1-45, IGHV3-20, IGHV3-48, IGHV3-49, IGHV4-4, and IGHV5-51) in the IGH region, were differentially expressed between the two groups. Conclusions: Camrelizumab with platinum-based chemotherapy is effective and well-tolerated as first-line treatment in advanced ESCC. IR sequencing may provide insights into the underlying mechanisms influencing treatment response. Clinical trial information: ChiCTR2000037942. Objective response and disease response. Efficacy evaluation Total (N=88) Camrelizumab plus T（n=69） Camrelizumab plus FP (n=19) p 1-year PFS rate 50/88 (56.8%) 39/69 (56.5%) 11/19 (57.9%) 1.000 1-year OS rate 60/88 (68.2%) 47/69 (68.1%) 13/19 (68.4%) 1.000 ORR 57/88 (64.8%) 43/69 (62.3%) 11/19 (57.9%) 0.793 DCR 81/88 (91.1%) 63/69 (91.3%) 15/19 (79.0%) 0.213 ORR group, n (%) 54/88 (61.4%) 43/69 (62.3%) 11/19 (57.89%) 0.793 Non-ORR Group, n (%) 34/88 (38.6%) 26/69 (37.7%) 8/19 (42.1%) 1.000 2-year PFS rate 38/88 (43.2%) 30/69 (43.5%) 8/19 (42.1%) 1.000 2-year OS rate 42/88 (47.7%) 33/69 (47.8%) 9/19 (47.4%) 1.000 *p<0.05, a statistically difference.