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BACKGROUND AND AIMS:This multicenter retrospective study in Japan aimed to investigate the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in patients with unresectable hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS:A total of 377 patients with HCC and treated with Dur/Tre across 30 institutions in Japan were included in this multicenter study. Time-dependent receiver operating characteristic (ROC) analysis was performed to determine the optimal LMR cut-off value. Hazard ratio (HR) spline curve analysis was used to identify the optimal LMR range for predicting progression-free survival (PFS) and overall survival (OS). RESULTS:Time-dependent ROC analysis identified an optimal LMR cut-off value of 2.52 for predicting median OS. Multivariate analysis demonstrated that an LMR of ≥ 2.52 was independently associated with superior PFS (HR: 0.777) and OS (HR: 0.657). The median PFS was 2.6 months in patients with an LMR of < 2.52, compared with 3.5 months in those with an LMR of ≥ 2.52 (p = 0.022). The median OS was 12.8 months in patients with an LMR of < 2.52, compared with 23.4 months in those with an LMR of ≥ 2.52 (p < 0.001). The disease control rate was significantly higher in the high LMR group (p = 0.032). The HR spline curve analysis revealed that an LMR range of approximately 1.8-2.6 represents an optimal cut-off for predicting both PFS and OS. CONCLUSIONS:LMR is a readily accessible prognostic biomarker for both PFS and OS in patients with unresectable HCC treated with Dur/Tre, and may serve as a practical tool for risk stratification in clinical practice.
AIM:We aimed to determine the associations between the pretreatment Advanced Lung Cancer Inflammation Index (ALI) and survival outcomes in patients with unresectable hepatocellular carcinoma (u-HCC) who received atezolizumab plus bevacizumab (Atez/Bev). METHODS:This retrospective study analyzed 563 patients with u-HCC who were treated with Atez/Bev (Sept 2020-Dec 2024). The ALI was calculated according to Body Mass Index × serum albumin level/neutrophil-to-lymphocyte ratio. Associations between ALI and overall survival (OS) and progression-free survival (PFS) were evaluated by Cox proportional hazards regression analysis. RESULTS:An ALI cutoff value of 27.04, determined by receiver operating characteristic curve analysis, was used to classify patients into low- and high-ALI groups. High-ALI patients had longer median OS (26.1 vs. 13.7 months, p < 0.001) and PFS (9.3 vs. 5.2 months, p < 0.001), and a higher disease control rate (82.5% vs. 69.1%, p < 0.001) compared to low-ALI patients. Multivariate Cox regression analysis confirmed that a high ALI value was a significant prognostic marker for OS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.54-0.88, p = 0.003) and PFS (HR: 0.75, 95% CI: 0.61-0.92, p = 0.006). Subgroup analyses showed that the trend toward improved outcomes was consistent for high ALI values in all clinically relevant subgroups. CONCLUSIONS:A high pretreatment ALI value was associated with improved survival and disease control in u-HCC patients receiving Atez/Bev, underscoring its potential utility as a prognostic marker for clinical management and further studies.
ABSTRACT Durvalumab plus tremelimumab (Dur/Tre) is the first‐line treatment for unresectable hepatocellular carcinoma (uHCC). Immune‐mediated adverse events (imAEs) are common; however, the impact of specific imAE types on treatment persistence and outcomes remains unclear. This study evaluated the clinical features and prognostic implications of common imAEs during Dur/Tre therapy. This multicenter retrospective analysis included 351 patients with uHCC treated with Dur/Tre (January 2023 and February 2025), of whom 69 developed imAEs and had a follow up period of > 1 month. Baseline characteristics, period to onset and severity of imAEs, corticosteroid use, treatment continuation and subsequent therapies, progression‐free survival (PFS) and overall survival (OS) were analyzed according to imAE types. Among 69 patients, 34 developed colitis, 19 developed hepatitis and 16 developed endocrine disorders. The median age was 72 years, with 13% classified as Child‐Pugh B. The median period to imAE onset was 0.75 months (interquartile range, 0.38–1.25). Steroids at a dose equivalent to > 20 mg of prednisolone were administered to 46 patients (66.7%). Two‐thirds of the patients continued Dur/Tre despite imAE onset. Colitis occurred the earliest (median 0.54 months) and had the highest steroid requirement (82.4%), frequently resulting in treatment interruption. Endocrine disorders showed the highest continuation rate (75%). Although not statistically significant in PFS (median 11.2 months: 95% CI, 1.96–not achieved (NA), p = 0.450) and OS (95% CI, NA–NA, p = 0.134), compared with colitis (PFS; 4.3 months, OS; not reached) and hepatitis (PFS; 3.4 months, OS: 14.6 months). These findings should be interpreted cautiously given the small sample size. Subsequent systemic or locoregional therapies, including tyrosine kinase inhibitors, atezolizumab plus bevacizumab and interventional therapies, were administered to more than 65% of the patients. In Dur/Tre therapy, imAE impact varied by type; endocrine disorders are linked to better treatment continuation and prognosis, whereas colitis and hepatitis often lead to treatment interruption. Trial Registration: Takasaki General Medical Center (IRB No. TGMC2024–03)
Abstract Fucosylated haptoglobin (Fuc-Hp) has been recognized as a cancer-associated glycoform. We previously established a monoclonal antibody, 10-7G mAb, which detects both Fuc-Hp and its precursor prohaptoglobin (proHp). Recent studies have suggested that proHp itself may serve as a cancer-associated biomarker with clinical implications distinct from those of Fuc-Hp. Importantly, proHp is produced during inflammation and cancer progression and may exert biological activities different from mature haptoglobin (Hp). These observations highlight the need for a reagent that can specifically detect proHp. However, to date, no antibody strictly specific to proHp has been available. In this study, we generated a monoclonal antibody, 21-4F mAb, which specifically recognizes human proHp without cross-reactivity to mature Hp. Using 21-4F mAb, we developed a proHp-specific enzyme-linked immunosorbent assay and integrated it with assays for several types of Hp, enabling independent quantification of three Hp-related isoforms. Serum analyses of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer revealed distinct alterations among these isoforms, and their combined use provided the highest diagnostic performance. Taken together, 21-4F mAb offers a novel analytical tool for investigating the pathophysiological significance of proHp and may contribute to the development of refined biomarker panels for cancer diagnosis and disease monitoring.
BACKGROUND AND AIM:This study evaluated clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre) in routine practice, stratified by whether they fulfilled the eligibility criteria of the phase 3 HIMALAYA trial. METHODS:A total of 412 patients with unresectable HCC receiving Dur/Tre at 30 Japanese institutions were enrolled. Of these, 92 fulfilled the HIMALAYA trial eligibility criteria (HIMALAYA group) and 320 did not (non-HIMALAYA group). RESULTS:Median progression-free survival (PFS) was 5.4 months in the HIMALAYA group and 3.0 months in the non-HIMALAYA group (p = 0.012). Multivariable analysis identified body mass index ≥ 25 kg/m2 (hazard ratio [HR], 0.780; 95% confidence interval [CI], 0.612-0.993; p = 0.044) and portal vein invasion (HR, 1.509; 95% CI, 1.049-2.170; p = 0.027) as independent predictors of PFS. Median overall survival (OS) was 19.4 months in the HIMALAYA group versus 15.4 months in the non-HIMALAYA group (p = 0.014). Multivariable analysis showed Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.878; 95% CI, 1.253-2.814; p = 0.002) and albumin-bilirubin grade ≥ 2 (HR, 2.032; 95% CI, 1.319-3.318; p = 0.001) as independent determinants of OS. Any-grade endocrine dysfunction occurred in 13 (14.1%) and 21 (6.6%) patients (p = 0.030), with grade ≥ 3 events in 5 (5.4%) and 2 (0.6%), respectively (p = 0.007). Subgroup analysis suggested that non-HIMALAYA patients with ALBI grade 1 may have OS comparable to the HIMALAYA group. CONCLUSIONS:Patients fulfilling the HIMALAYA trial eligibility criteria and those who did not but had preserved hepatic function demonstrated favorable survival outcomes with Dur/Tre.
