Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal and invasive cancer. Targeted and immunotherapies are the primary treatment options for unresectable advanced HCC. There are no recognized and consistent systemic follow-up treatments for patients with HCC who experience disease progression after first-line targeted therapies and immune checkpoint inhibitors (ICIs). According to a few studies, lenalidomide is an immunomodulatory drug that has the potential to be an effective treatment for patients who have progressed after treatment with targeted drugs and ICIs. CASE SUMMARY: This article focuses on a patient with HCC whose disease progressed after first-line targeted therapy and ICI therapy combined with lenalidomide as second-line therapy on the basis of the original targeted and ICI regimens, resulting in a favorable oncologic outcome with acceptable toxicity. The progression-free survival (PFS) of the patients in this study reached 3 years, which is much longer than that previously reported, and no progression has occurred thus far. CONCLUSIONS: This case implies that in patients with hepatocellular carcinoma who have failed first-line targeted therapy and ICIs, targeted therapy and ICIs can be restarted with the addition of lenalidomide, with surprising results.