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
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | JGH Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jgh3.70123 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849721869230407680 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Yuta Inoue |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2905b51efb0d47ec9af4a563f3a6c39a |
| institution | DOAJ |
| issn | 2397-9070 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | JGH Open |
| spelling | doaj-art-2905b51efb0d47ec9af4a563f3a6c39a2025-08-20T03:11:31ZengWileyJGH Open2397-90702025-02-0192n/an/a10.1002/jgh3.70123Higher 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 CarcinomaYuta Inoue0Yoshihiko Yano1Saeko Kushida2Seiya Hirohata3Seitetsu Yoon4Eiichiro Yasutomi5Hirotaka Hirano6Soo Ki Kim7Ryutaro Yoshida8Yoshihide Ueda9Kenji Momose10Hiroki Hayashi11Takuo Kado12Katsuhisa Nishi13Hidenori Tanaka14Tomomitsu Matono15Atsushi Yamamoto16Hiroshi Tei17Chiharu Nishioka18Yosuke Yagi19Shoji Tamura20Tatsuya Sakane21Mayumi Ehara22Miki Kawano23Jun Kitadai24Takanori Matsuura25Yuuki Shiomi26Shohei Komatsu27Takumi Fukumoto28Toshifumi Tada29Yuzo Kodama30Division of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanHyogo Prefectural Hyogo Cancer Center Akashi Hyogo JapanHyogo Prefectural Kakogawa Medical Center Kakogawa Hyogo JapanHyogo Prefectural Kakogawa Medical Center Kakogawa Hyogo JapanHyogo Prefectural Kakogawa Medical Center Kakogawa Hyogo JapanYodogawa Christian Hospital Osaka JapanKobe Asahi Hospital Kobe Hyogo JapanKakogawa Central City Hospital Kakogawa Hyogo JapanKakogawa Central City Hospital Kakogawa Hyogo JapanOsaka Saiseikai Nakatsu Hospital Osaka JapanKitaharima Medical Center Ono Hyogo JapanAkashi Medical Center Akashi Hyogo JapanHyogo Prefectural Awaji Medical Center Sumoto Hyogo JapanSanda City Hospital Sanda Hyogo JapanHyogo Prefectural Harima‐Himeji General Medical Center Himeji Hyogo JapanHyogo Prefectural Harima‐Himeji General Medical Center Himeji Hyogo JapanKobe City Medical Center General Hospital Kobe Hyogo JapanKonan Medical Center Kobe Hyogo JapanShiso Municipal Hospital Shiso Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanDivision of Gastroenterology Kobe University Graduate School of Medicine Kobe City Hyogo JapanABSTRACT 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.https://doi.org/10.1002/jgh3.70123absolute lymphocyte countdes‐γ‐carboxyprothrombinhepatocellular carcinomatremelimumab and durvalumab |
| spellingShingle | 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 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 JGH Open absolute lymphocyte count des‐γ‐carboxyprothrombin hepatocellular carcinoma tremelimumab and durvalumab |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | absolute lymphocyte count des‐γ‐carboxyprothrombin hepatocellular carcinoma tremelimumab and durvalumab |
| url | https://doi.org/10.1002/jgh3.70123 |
| work_keys_str_mv | AT yutainoue higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT yoshihikoyano higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT saekokushida higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT seiyahirohata higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT seitetsuyoon higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT eiichiroyasutomi higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT hirotakahirano higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT sookikim higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT ryutaroyoshida higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT yoshihideueda higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT kenjimomose higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT hirokihayashi higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT takuokado higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT katsuhisanishi higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT hidenoritanaka higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT tomomitsumatono higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT atsushiyamamoto higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT hiroshitei higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT chiharunishioka higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT yosukeyagi higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT shojitamura higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT tatsuyasakane higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT mayumiehara higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT mikikawano higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT junkitadai higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT takanorimatsuura higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT yuukishiomi higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT shoheikomatsu higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT takumifukumoto higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT toshifumitada higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma AT yuzokodama higherabsolutelymphocytecountsandlowerdesgcarboxyprothrombinlevelsaftertreatmentinitiationareassociatedwiththeclinicalefficacyoftremelimumabplusdurvalumabcombinationtherapyforhepatocellularcarcinoma |