ABSTRACT
BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Propensity Score , Retrospective Studies , Liver Neoplasms/drug therapyABSTRACT
Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after solid organ transplantation. Reduction of immunosuppression (RI) is accepted as a first step treatment with a long-term complete response rate observed in 23-50% of patients. Chemotherapy for diseases refractory to RI is based on small cohorts treated with different regimens. This paper reports on 10 consecutive cases of PTLD after liver transplantation. The median time from transplantation to PTLD diagnosis was 5 years. PTLD was frequently extranodal involving the transplanted liver. Seven monomorphic PTLD, 2 polymorphic and one Hodgkin disease were observed. Epstein Barr virus was present in tumour tissue only in one case. Initial therapy included RI in all patients. Chemotherapy was used in eight patients. No treatment-related mortality was observed and no patient developed graft rejection during chemotherapy. At a median follow-up period of 25 months, 6 of the 10 patients were alive and without evidence of disease.
Subject(s)
Liver Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Female , Herpesvirus 4, Human/isolation & purification , Humans , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/mortality , Male , Middle Aged , Risk Factors , Rituximab , Survival RateABSTRACT
Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining 20, the efficacy and safety of a weekly anthracycline-based chemotherapy were assessed. Sixteen patients obtained a complete remission. One death was related to treatment. With a median follow-up of 36 months, 3-year overall survival was 63.3% and 57% for the entire group and the chemotherapy-treated group, respectively. Moreover, 4 second neoplasms were observed in the chemotherapeutic group. In this study, we demonstrated that most PTLD need other treatment than RI and a weekly regimen is manageable and has a favourable impact on long-term survival.