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

被引：0

作者：

Inoue, Yuta ^{[1
]}

Yano, Yoshihiko ^{[1
]}

Kushida, Saeko ^{[2
]}

Hirohata, Seiya ^{[3
]}

Yoon, Seitetsu ^{[3
]}

Yasutomi, Eiichiro ^{[3
]}

Hirano, Hirotaka ^{[4
]}

Kim, Soo Ki ^{[5
]}

Yoshida, Ryutaro ^{[6
]}

Ueda, Yoshihide ^{[6
]}

Momose, Kenji ^{[7
]}

Hayashi, Hiroki ^{[8
]}

Kado, Takuo ^{[9
]}

Nishi, Katsuhisa ^{[10
]}

Tanaka, Hidenori ^{[11
]}

Matono, Tomomitsu ^{[12
]}

Yamamoto, Atsushi ^{[12
]}

Tei, Hiroshi ^{[13
]}

Nishioka, Chiharu ^{[14
]}

Yagi, Yosuke ^{[15
]}

Tamura, Shoji ^{[1
]}

Sakane, Tatsuya ^{[1
]}

Ehara, Mayumi ^{[1
]}

Kawano, Miki ^{[1
]}

Kitadai, Jun ^{[1
]}

Matsuura, Takanori ^{[1
]}

Shiomi, Yuuki ^{[1
]}

Komatsu, Shohei ^{[16
]}

Fukumoto, Takumi ^{[16
]}

Tada, Toshifumi ^{[1
]}

Kodama, Yuzo ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Div Gastroenterol, Kobe, Hyogo, Japan

[2] Hyogo Canc Ctr, Akashi, Hyogo, Japan

[3] Hyogo Prefectural Kakogawa Med Ctr, Kakogawa, Hyogo, Japan

[4] Yodogawa Christians Hosp, DEPT PEDIATR, OSAKA, Japan

[5] Kobe Asahi Hosp, Kobe, Hyogo, Japan

[6] Kakogawa Cent City Hosp, Kakogawa, Hyogo, Japan

[7] Osaka Saiseikai Nakatsu Hosp, Osaka, Japan

[8] Kitaharima Med Ctr, Ono, Hyogo, Japan

[9] Akashi Med Ctr, Akashi, Hyogo, Japan

[10] Hyogo Prefectural Awaji Med Ctr, Sumoto, Hyogo, Japan

[11] Sanda City Hosp, Sanda, Hyogo, Japan

[12] Hyogo Prefectural Harima Himeji Gen Med Ctr, Himeji, Hyogo, Japan

[13] Kobe City Med Ctr Gen Hosp, Kobe, Hyogo, Japan

[14] Konan Med Ctr, Kobe, Hyogo, Japan

[15] Shiso Municipal Hosp, Shiso, Hyogo, Japan

[16] Kobe Univ, Grad Sch Med, Div Hepatobiliary Pancreat Surg, Kobe, Hyogo, Japan

来源：

JGH OPEN | 2025年 / 9卷 / 02期

关键词：

absolute lymphocyte count; des-gamma-carboxyprothrombin; hepatocellular carcinoma; tremelimumab and durvalumab; CARBOXY PROTHROMBIN; ADVANCED MELANOMA; SORAFENIB; CHEMOTHERAPY; IPILIMUMAB;

D O I：

10.1002/jgh3.70123

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and AimsTremelimumab 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.MethodsSeventy 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.ResultsThe 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-gamma-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.ConclusionHigher ALC and lower DCP levels after treatment initiation were associated with the clinical efficacy of Dur/Tre for advanced HCC.

引用

页数：8

共 25 条

[1]

Abou-Alfa GK, 2022, NEJM EVID, V1, DOI 10.1056/EVIDoa2100070

[2] Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].

Bray, Freddie ;

Laversanne, Mathieu ;

Sung, Hyuna ;

Ferlay, Jacques ;

Siegel, Rebecca L. ;

Soerjomataram, Isabelle ;

Jemal, Ahmedin .

CA-A CANCER JOURNAL FOR CLINICIANS, 2024, 74 (03) :229-263

[3] Approaches to treat immune hot, altered and cold tumours with combination immunotherapies [J].

Galon, Jerome ;

Bruni, Daniela .

NATURE REVIEWS DRUG DISCOVERY, 2019, 18 (03) :197-218

[4] Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update [J].

Gordan, John D. ;

Kennedy, Erin B. ;

Abou-Alfa, Ghassan K. ;

Beal, Eliza ;

Finn, Richard S. ;

Gade, Terence P. ;

Goff, Laura ;

Gupta, Shilpi ;

Guy, Jennifer ;

Hoang, Hang T. ;

Iyer, Renuka ;

Jaiyesimi, Ishmael ;

Jhawer, Minaxi ;

Karippot, Asha ;

Kaseb, Ahmed O. ;

Kelley, R. Kate ;

Kortmansky, Jeremy ;

Leaf, Andrea ;

Remak, William M. ;

Sohal, Davendra P. S. ;

Taddei, Tamar H. ;

Woods, Andrea Wilson ;

Yarchoan, Mark ;

Rose, Michal G. .

JOURNAL OF CLINICAL ONCOLOGY, 2024, 42 (15) :1830-1850

[5] Concomitant Antibiotic Use and Survival in Urothelial Carcinoma Treated with Atezolizumab [J].

Hopkins, Ashley M. ;

Kichenadasse, Ganessan ;

Karapetis, Christos S. ;

Rowland, Andrew ;

Sorich, Michael J. .

EUROPEAN UROLOGY, 2020, 78 (04) :540-543

[6] Hepatic arterial infusion chemotherapy with cisplatin and sorafenib in hepatocellular carcinoma patients unresponsive to transarterial chemoembolization: A propensity score-based weighting [J].

Kondo, Masaaki ;

Morimoto, Manabu ;

Ishii, Tomohiro ;

Nozaki, Akito ;

Fukuda, Hiroyuki ;

Numata, Kazushi ;

Kobayashi, Satoshi ;

Ohkawa, Shinichi ;

Hidaka, Hisashi ;

Nakazawa, Takahide ;

Shibuya, Akitaka ;

Okuse, Chiaki ;

Suzuki, Michihiro ;

Sakamaki, Kentaro ;

Morita, Satoshi ;

Maeda, Shin ;

Tanaka, Katsuaki .

JOURNAL OF DIGESTIVE DISEASES, 2015, 16 (03) :143-151

[7] Single-Institution Experience With Ipilimumab in Advanced Melanoma Patients in the Compassionate Use Setting Lymphocyte Count After 2 Doses Correlates With Survival [J].

Ku, Geoffrey Y. ;

Yuan, Jianda ;

Page, David B. ;

Schroeder, Sebastian E. A. ;

Panageas, Katherine S. ;

Carvajal, Richard D. ;

Chapman, Paul B. ;

Schwartz, Gary K. ;

Allison, James P. ;

Wolchok, Jedd D. .

CANCER, 2010, 116 (07) :1767-1775

[8] Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2) [J].

Kudo, Masatoshi ;

Finn, Richard S. ;

Morimoto, Manabu ;

Rau, Kun-Ming ;

Ikeda, Masafumi ;

Yen, Chia-Jui ;

Galle, Peter R. ;

Llovet, Josep M. ;

Daniele, Bruno ;

Lim, Ho Yeong ;

McIlwain, David W. ;

Yoshikawa, Reigetsu ;

Nakamura, Kenichi ;

Liang, Kun ;

Wang, Chunxiao ;

Abada, Paolo ;

Widau, Ryan C. ;

Zhu, Andrew X. .

LIVER CANCER, 2021, 10 (05) :451-460

[9] Hepatocellular carcinoma [J].

Llovet, Josep M. ;

Kelley, Robin Kate ;

Villanueva, Augusto ;

Singal, Amit G. ;

Pikarsky, Eli ;

Roayaie, Sasan ;

Lencioni, Riccardo ;

Koike, Kazuhiko ;

Zucman-Rossi, Jessica ;

Finn, Richard S. .

NATURE REVIEWS DISEASE PRIMERS, 2021, 7 (01)

[10] Real-world efficacy and safety of durvalumab-tremelimumab as second-line systemic therapy after atezolizumab-bevacizumab in unresectable hepatocellular carcinoma [J].

Miura, Ryoichi ;

Ono, Atsushi ;

Yano, Shigeki ;

Amioka, Kei ;

Naruto, Kensuke ;

Yamaoka, Kenji ;

Fujii, Yasutoshi ;

Uchikawa, Shinsuke ;

Fujino, Hatsue ;

Nakahara, Takashi ;

Murakami, Eisuke ;

Kawaoka, Tomokazu ;

Miki, Daiki ;

Tsuge, Masataka ;

Hayes, C. Nelson ;

Oka, Shiro .

MEDICINE, 2024, 103 (34) :e39289

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