Exploration of Personalized Treatment for Advanced Hepatocellular Carcinoma: Combination Therapy of Selinexor, Palbociclib, and Pembrolizumab with Umbilical Cord Blood NK Cells.

Objective: To report the efficacy and safety of combination therapy with selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells for advanced hepatocellular carcinoma (HCC).Advanced HCC has a poor prognosis and limited effective treatment options. Exploring personalized combination treatment strategies is critically important for improving outcomes in patients with advanced HCC. This study aims to provide preliminary evaluation of the clinical effectiveness and safety of this combination regimen in this high-risk population, and lay the groundwork for larger studies to bring more treatment choices to patients with advanced HCC.

Methods: A 67-year-old male patient with advanced HCC and multiple metastases was treated with palbociclib 75mg on days 1-14 of a 28-day cycle, pembrolizumab 200mg intravenous infusion, selinexor 40mg weekly, and umbilical cord blood NK cell (12×109 cells) infusion on days 1, 14, 28 and 42. Imaging examinations and tumor marker detection were performed before and after two cycles of treatment to evaluate response.

Results: After two cycles of combination treatment, follow-up PET-CT showed partial response with the liver tumors reduced in size by approximately 60%, lung metastases reduced by approximately 90%, and FDG uptake decreased more than 90% in lymph nodes and bone metastases. The AFP level decreased compared to baseline. Liver function tests including albumin, bilirubin and prothrombin time improved. The patient's performance status also improved from ECOG 2 to ECOG 1.

Conclusions: This case report describes preliminary signals that the combination of selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells may warrant further investigation for the treatment of advanced HCC. Objective response was observed based on standardized response criteria. However, due to the limitations of a single-arm case study design, definitive conclusions cannot be drawn regarding the efficacy or safety profile of this personalized combination approach. Larger and more robust clinical trials are needed to fully validate if this treatment strategy can achieve clinical benefit for advanced HCC. Future studies should aim to elucidate potential biomarkers that may help identify patients most likely to respond to this combination regimen. Exploring optimal patient selection criteria could also help maximize clinical benefit. Further research is warranted to continue exploring precision medicine combinations involving immunotherapy, targeted agents and cellular therapies for advanced HCC.