Higher Absolute Lymphocyte Counts and Lower Des-γ-Carboxyprothrombin Levels After Treatment Initiation Are Associated With the Clinical Efficacy of Tremelimumab Plus Durvalumab Combination Therapy for Hepatocellular Carcinoma

IF 1.7 Q3 GASTROENTEROLOGY & HEPATOLOGY
JGH Open Pub Date : 2025-02-20 DOI:10.1002/jgh3.70123
Yuta Inoue, Yoshihiko Yano, Saeko Kushida, Seiya Hirohata, Seitetsu Yoon, Eiichiro Yasutomi, Hirotaka Hirano, Soo Ki Kim, Ryutaro Yoshida, Yoshihide Ueda, Kenji Momose, Hiroki Hayashi, Takuo Kado, Katsuhisa Nishi, Hidenori Tanaka, Tomomitsu Matono, Atsushi Yamamoto, Hiroshi Tei, Chiharu Nishioka, Yosuke Yagi, Shoji Tamura, Tatsuya Sakane, Mayumi Ehara, Miki Kawano, Jun Kitadai, Takanori Matsuura, Yuuki Shiomi, Shohei Komatsu, Takumi Fukumoto, Toshifumi Tada, Yuzo Kodama
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Abstract

Background and Aims

Tremelimumab plus durvalumab (Dur/Tre) combination therapy is now a first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Because systemic therapy is not effective in some patients, it is clinically important to identify factors that could predict the response to treatment at an early stage. We investigated the factors associated with the response to Dur/Tre for advanced HCC in a clinical setting.

Methods

Seventy patients (median age 74 years; 61 men) who received Dur/Tre between March 2023 and September 2024 were analyzed. We examined the factors associated with the treatment response, including pretreatment factors and factors early in treatment.

Results

The median treatment duration was 77.5 (interquartile range [IQR] 28–187) days. The overall response and disease control rates were 25.8% and 58.1%, respectively. The median (IQR) progression-free survival (PFS) and overall survival (OS) were 82 (61–133) and 415 (337–NA) days, respectively. Multivariable analysis revealed that higher absolute lymphocyte count (ALC) and lower des-γ-carboxyprothrombin (DCP) levels were significantly associated with PFS. Receiver operating characteristic curve analysis showed that the cutoff value for ALC after 4 weeks of treatment in relation to clinical efficacy was 1125/mm3. A log-rank test using the Kaplan–Meier method showed that OS was significantly longer in patients with ALC above the cutoff and in patients whose DCP levels decreased after starting treatment.

Conclusion

Higher ALC and lower DCP levels after treatment initiation were associated with the clinical efficacy of Dur/Tre for advanced HCC.

Abstract Image

治疗开始后较高的绝对淋巴细胞计数和较低的Des-γ-羧凝血酶原水平与Tremelimumab加Durvalumab联合治疗肝癌的临床疗效相关
背景和目的Tremelimumab + durvalumab (Dur/Tre)联合治疗目前是晚期肝细胞癌(HCC)的一线全身治疗。由于全身治疗对一些患者无效,因此在临床早期确定能够预测治疗反应的因素是很重要的。我们在临床环境中研究了与Dur/Tre治疗晚期HCC疗效相关的因素。方法70例患者(中位年龄74岁;对2023年3月至2024年9月期间接受Dur/Tre治疗的61名男性进行了分析。我们检查了与治疗反应相关的因素,包括预处理因素和治疗早期因素。结果中位治疗时间为77.5天(四分位数间距[IQR] 28 ~ 187) d。总有效率为25.8%,疾病控制率为58.1%。中位(IQR)无进展生存期(PFS)和总生存期(OS)分别为82(61-133)天和415 (337-NA)天。多变量分析显示,较高的绝对淋巴细胞计数(ALC)和较低的des-γ-羧基凝血酶原(DCP)水平与PFS显著相关。受试者工作特征曲线分析显示,治疗4周后ALC与临床疗效的临界值为1125/mm3。Kaplan-Meier法的log-rank检验显示,ALC高于临界值的患者和开始治疗后DCP水平下降的患者的OS明显更长。结论治疗开始后ALC升高、DCP降低与Dur/Tre治疗晚期HCC的临床疗效相关。
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来源期刊
JGH Open
JGH Open GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
3.40
自引率
0.00%
发文量
143
审稿时长
7 weeks
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