Safety and Efficacy of Locoregional Treatment during Immunotherapy with Nivolumab for Hepatocellular Carcinoma: A Retrospective Study of 41 Interventions in 29 Patients

Abstract

Materials and Methods: A single-center retrospective review included 29 patients undergoing 41 LRTs-transarterial chemoembolization or yttrium-90 transarterial radioembolization-60 days before or concurrently with nivolumab. Demographic, clinical, and laboratory values and adverse events were reviewed before and after nivolumab initiation and after each LRT. Treatment response and time to progression were assessed using Modified Response Evaluation Criteria in Solid Tumors. Clinical events, including nivolumab termination, death, and time of last follow-up, were assessed.Results: Over a median nivolumab course of 8.1 months (range, 1.0-30) with a median of 14.2 2-week cycles (range, 1-53), predominantly Child-Pugh A (22/29) patients-12 Barcelona Clinic Liver Cancer (BCLC) B and 17 BCLC C-underwent 20 transarterial chemoembolization and 21 transarterial radioembolization LRTs at a median of 67 days (range, 48-609) after nivolumab initiation. Ten patients underwent multiple LRTs. During a median follow-up of 11.5 months (range, 1.8-35.1), no grade III/IV adverse events attributable to nivolumab were observed. There were five instances of grade III/IV hypoalbuminemia or hyperbilirubinemia within 3 months after LRT. There were no nivolumab-related deaths, and 30-day mortality after LRT was 0%.

Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression

“…Similar to the study of Qin et al, the most common AEs in this study was also RCCEP [16]. However, the AEs incidence of grade III or more with camrelizumab seemed to be lower than that with other ICIs [14,15], suggesting that camrelizumab is safe for the treatment of HCC with UP after TACE.…”

“…It is reported that TACE can promote tumor-speci c CD8 + T cell response by killing HCC cells and causing the release of tumorassociated antigens [17]. As suggested by the theoretical advantages, both Zhan et al [15] and Marinelli et al [14] demonstrated the e cacy of transarterial embolization combined with ICIs in the treatment of HCC. Similarly, this study also con rmed that TACE combined with ICI was superior to ICI monotherapy.…”

“…Immune checkpoint inhibitors (ICIs) that reverse immune exhaustion have been shown to be effective in HCC, which were used alone and in combination with TACE in treatment of intermediate and advanced HCC [13][14][15]. Recently, camrelizumab, an anti-PD-1 monoclonal antibody, was approved in China as a second-line treatment for unresectable HCC.…”

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

“…Based on previous observations, several pilot studies have evaluated the possibility of LRTs combined with ICBs in patients with HCC. In a single-center retrospective study, LRTs, including TACE or TARE combined with nivolumab, were tolerated in a small number of patients with intermediate or advanced HCC without deterioration of liver function [ 99 ], indicating that LRTs with ICBs is a safe strategy. In another retrospective study, TARE combined with ICBs was shown to be safe and tolerable [ 100 ].…”

Interventional Radiology Image-Guided Locoregional Therapies (LRTs) and Immunotherapy for the Treatment of HCC

“…Regarding the safety of LRTs combined with immunotherapy, the available data seem to point towards an acceptable safety profile; for example, TARE plus nivolumab showed a similar safety profile when compared to TARE alone [ 195 ], tremelimumab in combination with ablation proved to be safe for the treatment of advanced HCC [ 193 ], no significant adverse reaction was found when combining RFA with cellular immunotherapy in HCC patients [ 194 ].…”