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 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.

Keywords: absolute lymphocyte count; des‐γ‐carboxyprothrombin; hepatocellular carcinoma; tremelimumab and durvalumab.

FIGURE 1

Kaplan–Meier analysis of PFS and OS. Kaplan–Meier curves of PFS (a) and OS (b) according to disease control. The red lines indicate patients with CR/PR/SD and the black lines indicate patients with PD. Kaplan–Meier curves for PFS (c) and OS (d) according to the overall response. The red lines indicate patients with CR/PR and the black lines indicate patients with SD/PD. CR, complete response; OS, overall survival; PD, progressive disease; PFS, progression‐free survival; PR, partial response; SD, stable disease.

FIGURE 2

(a) Receiver operating characteristic curve analysis of the ALC at 4 weeks after the start of treatment for clinical efficacy. (b) Kaplan–Meier curves for OS according to the ALC at 4 weeks after the start of treatment. The red line indicates patients with an ALC above the cutoff (i.e., ≥ 1125/mm³) and the black line indicates patients with an ALC below the cutoff (i.e., < 1125/mm³). (c) Kaplan–Meier curves of OS according to the change in DCP at 4 weeks. The red line indicates patients whose DCP level increased at 4 weeks and the black line indicates patients whose DCP level decreased at 4 weeks. ALC, absolute lymphocyte count; AUROC, area under the ROC curve; DCP, des‐γ‐carboxy prothrombin; OS, overall survival; ROC, receiver operating characteristic.