Complete Remission of Hepatocellular Carcinoma With Atezolizumab and Bevacizumab Following Prior B-cell Depletion

Immune checkpoint inhibitors (ICIs) are established therapies for unresectable hepatocellular carcinoma (HCC), with atezolizumab/bevacizumab and durvalumab/tremelimumab demonstrating clinical efficacy. Beyond activating CD8+ T cells, anti-PD(L)-1 therapies stimulate humoral immunity through B-cell activation and tertiary lymphoid structures. However, ICIs can also cause immune-related adverse events (irAEs), some managed with anti-CD20 therapy, raising concerns about whether B-cell depletion impacts subsequent ICI efficacy. This report presents a novel case of dual malignancies-diffuse large B-cell lymphoma (DLBCL) and HCC-in a patient in their 70s successfully treated with sequential R-CHOP and atezolizumab/bevacizumab. Following 6 cycles of R-CHOP for DLBCL, the patient achieved a complete metabolic response but developed recurrent HCC. Flow cytometry revealed B-cell depletion and hypogammaglobulinemia after R-CHOP. Upon initiation of atezolizumab/bevacizumab, AFP levels rapidly declined, and complete tumor remission was confirmed. Notably, NK cell percentages increased following ICI therapy, suggesting enhanced immune activation. This case demonstrates that prior rituximab-induced B-cell depletion does not impair the efficacy of anti-PD-L1 therapy in HCC and highlights the potential role of NK cells in mediating antitumor immunity during immunotherapy.