Early Changes in Lymphocyte Counts Predict Clinical Outcomes in Hepatocellular Carcinoma Treated With Durvalumab Plus Tremelimumab

ABSTRACT Background Durvalumab plus tremelimumab (Dur/Tre) has shown promising efficacy in advanced hepatocellular carcinoma (HCC), but predictive biomarkers remain unclear. This study aimed to determine whether early changes in peripheral blood lymphocyte counts during Dur/Tre therapy can predict clinical outcomes. Methods In this multicenter retrospective study, we evaluated 299 patients with advanced HCC to assess whether early changes in peripheral blood lymphocyte counts predict clinical outcomes during Dur/Tre therapy. Changes in lymphocyte counts at 2 weeks after treatment initiation (2w‐Δlymphocyte) were analyzed in relation to objective response rate (ORR), progression‐free survival (PFS), and overall survival. Results Patients with a high‐2w‐Δlymphocyte (> +107/μL) demonstrated a significantly higher ORR (29.6% vs. 14.0%, p < 0.001) and longer PFS (4.3 vs. 2.8 months, p = 0.035) compared with those with a low‐2w‐Δlymphocyte (≤ +107/μL). Subgroup analyses showed that higher 2w‐Δlymphocyte values were associated with better PFS across modified albumin–bilirubin grades ( p = 0.011), Barcelona Clinic Liver Cancer stages ( p = 0.007), and baseline lymphocyte‐to‐monocyte ratio ( p < 0.001). Conclusions Early increases in peripheral blood lymphocyte counts, particularly 2w‐Δlymphocyte, may be associated with treatment response to Dur/Tre and provide complementary dynamic information to established prognostic factors. Although a favorable association with PFS was observed, this association was attenuated after propensity score matching. Further prospective studies are warranted to validate the clinical utility of 2w‐Δlymphocyte.

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Journal
Journal of Gastroenterology and Hepatology
Published
2026-10-05
DOI
https://doi.org/10.1111/jgh.70793
Primary Topic
Hepatocellular Carcinoma Treatment and Prognosis
Type
article
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article

Early Changes in Lymphocyte Counts Predict Clinical Outcomes in Hepatocellular Carcinoma Treated With Durvalumab Plus Tremelimumab

Hideki Kobara, Tomotake Shirono, Takanori Matsuura, Yasuto Takeuchi et al.
Journal of Gastroenterology and Hepatology
Hepatocellular Carcinoma Treatment and Prognosis
article

Early Changes in Lymphocyte Counts Predict Clinical Outcomes in Hepatocellular Carcinoma Treated With Durvalumab Plus Tremelimumab

Hideki Kobara, Tomotake Shirono, Takanori Matsuura, Yasuto Takeuchi, Takafumi Yamamoto, Norikazu Tanabe, Joji Tani, Yuki Kanayama, Naoki Yoshioka, Masahiro Sakata, Hisamitsu Miyaaki, Takeshi Hatanaka, Tetsuji Takayama, Yuichi Honma, Tetsu Tomonari, Shigeo Shimose, Nobuhiro Nakamoto, Tetsuya Yasunaka, Ryu Sasaki, Kyo Sasaki, Motoyuki Otsuka, Yuzo Kodama, Sohji Nishina, Atsushi Naganuma, Hiroki Kawashima, Nobuhito Taniki, Issei Saeki, Takanori Ito, Masaru Harada, Hideki Iwamoto, Taro Takami, Satoru Kakizaki, Takumi Kawaguchi, Takehito Naito, Satoshi Itano, Mamiko Takeuchi
article en

Abstract

ABSTRACT Background Durvalumab plus tremelimumab (Dur/Tre) has shown promising efficacy in advanced hepatocellular carcinoma (HCC), but predictive biomarkers remain unclear. This study aimed to determine whether early changes in peripheral blood lymphocyte counts during Dur/Tre therapy can predict clinical outcomes. Methods In this multicenter retrospective study, we evaluated 299 patients with advanced HCC to assess whether early changes in peripheral blood lymphocyte counts predict clinical outcomes during Dur/Tre therapy. Changes in lymphocyte counts at 2 weeks after treatment initiation (2w‐Δlymphocyte) were analyzed in relation to objective response rate (ORR), progression‐free survival (PFS), and overall survival. Results Patients with a high‐2w‐Δlymphocyte (> +107/μL) demonstrated a significantly higher ORR (29.6% vs. 14.0%, p < 0.001) and longer PFS (4.3 vs. 2.8 months, p = 0.035) compared with those with a low‐2w‐Δlymphocyte (≤ +107/μL). Subgroup analyses showed that higher 2w‐Δlymphocyte values were associated with better PFS across modified albumin–bilirubin grades ( p = 0.011), Barcelona Clinic Liver Cancer stages ( p = 0.007), and baseline lymphocyte‐to‐monocyte ratio ( p < 0.001). Conclusions Early increases in peripheral blood lymphocyte counts, particularly 2w‐Δlymphocyte, may be associated with treatment response to Dur/Tre and provide complementary dynamic information to established prognostic factors. Although a favorable association with PFS was observed, this association was attenuated after propensity score matching. Further prospective studies are warranted to validate the clinical utility of 2w‐Δlymphocyte.

Journal of Gastroenterology and Hepatology
Kurume University (JP), Yamaguchi University (JP), University of Occupational and Environmental Health Japan (JP), Kawasaki Medical School (JP), Kagawa University (JP), Keio University (JP), Okayama University Hospital (JP), National Hospital Organization Takasaki Medical Center (JP), Fukuyama City Hospital (JP), Kitakyushu Municipal Medical Center (JP), Japanese Red Cross Nagoya Daiichi Hospital (JP), Gunma Saiseikai Maebashi Hospital (JP), Kagawa University Hospital (JP), Anjo Kosei Hospital (JP), Toyohashi Municipal Hospital (JP), Nagasaki University (JP), Nagoya University (JP), Kobe University (JP), Tokushima University (JP)
Openalex Percentile: Top 13%
Hepatocellular Carcinoma Treatment and Prognosis
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