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.
Authors: Zhang Xiaoling , Zhao Wenqi , Du Yunyi , Su Fei , Wang Hui , Zhang Yuexiang , Ma Ning , Yang Wei , Yang Bo , Liu Min , Gao Yangjun , Yao Chunmei , Xu Ning , Wang Yu , Li Yongai , Song Guohua , Hu Wenqing , Zhao Jun 
Published: January 2025

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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.