Increased Spleen Volume in Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab in Comparison to Lenvatinib: A Retrospective Analysis

Introduction: We previously reported 2 cases of esophageal varices rupture during atezolizumab and bevacizumab (Atez/Bev) treatment, in which the spleen volume gradually increased. The aim of this retrospective study is to compare the chronological change in spleen volume of patients treated with Atez/Bev and lenvatinib (LEN). Methods: Seventy-two patients (Atez/Bev group, n = 26; LEN group, n = 46) were included in this retrospective study. The splenic parenchyma area was measured based on CT imaging. We used mixed-effect regression models with random intercepts to test the difference in the rate of change in spleen volume between the Atez/Bev and LEN groups. Results: The median age of the Atez/Bev and LEN groups was 74.0 (71.0-82.0) and 72.0 (67.5-76.0), respectively. About 80% patients were male. The mALBI grade was classified as 1, 2a, 2b, and 3 in 10 (38.5%), 6 (23.1%), 10 (38.5%), and zero (0.0%) patients, respectively, in the Atez/Bev group and 21 (45.7%), 9 (19.6%), 15 (32.6%), and 1 (2.2%) patient in the LEN group (p = 0.9). The median baseline neutrophil-to-lymphocyte ratio (NLR) was 2.61 (1.80-3.41) in the Atez/Bev group and 2.71 (1.76-3.67) in the LEN group (p = 1.0). The median baseline spleen volume was 185 (132-246) cm(3) in the Atez/Bev group and 231 (150-355) cm(3) in the LEN group. The spleen volume gradually increased during Atez/Bev treatment (2.41 cm(3) per week), while it was mostly consistent during LEN treatment (0.32 cm(3) per week). Among patients with mALBI grade 2b or 3, the spleen volume increased in the Atez/Bev group (2.99 cm(3) per week) and slightly decreased in the LEN group (0.82 cm(3) per week), without statistical significance (p = 0.07). Among patients with a baseline NLR of >2.68, the spleen volume increased at a rate of 2.57 cm(3) per week in the Atez/Bev group and decreased at a rate of 1.18 cm(3) per week in the LEN group. The difference in the slope of the two groups was statistically significant (p = 0.04). Discussion/Conclusion: Atez/Bev treatment could result in an increased spleen volume. Caution is required when managing patients treated with Atez/Bev, especially those with a high NLR.