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.