Efficacy and safety of recombinant human thrombopoietin (rhTPO) for thrombocytopenia induced by combinatorial interventional, targeted, and immunotherapy in hepatocellular carcinoma (SYNERGY-TPOACT): A retrospective cohort study.

e16250 Background: Combination regimens integrating interventional therapies (TACE/HAIC) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) are now established as the standard of care for advanced hepatocellular carcinoma (HCC). However, cumulative myelosuppression, specifically severe thrombocytopenia, frequently mandates dose reduction or treatment interruption, thereby compromising clinical outcomes. Although recombinant human thrombopoietin (rhTPO) is well-validated for chemotherapy-induced and immune thrombocytopenia, its utility in this specific setting remains ill- limited. We aimed to evaluate the efficacy and safety of rhTPO in HCC patients undergoing this combinatorial regimen. Methods: This retrospective cohort study assessed 60 HCC patients who developed thrombocytopenia (platelets ≤80×10⁹/L) sequelae to combined interventional, targeted, and immunotherapy at Guizhou Provincial People’s Hospital, China (March 2022-March 2025). All cohorts received subcutaneous rhTPO. The primary endpoint was the overall response rate (ORR), defined as complete response (CR: platelets ≥100×10⁹/L) or partial response (PR: absolute increment ≥25×10⁹/L). Secondary endpoints encompassed platelet kinetics, duration-response analysis, and safety profiles. Results: The cohort was characterized predominantly by BCLC stage C (50.0%) disease and Child-Pugh class B (55.0%) status. Baseline mean platelet count was 51.93×10⁹/L. Following rhTPO administration, the ORR reached 68.3% (CR:38.3%, PR:30.0%). The mean platelet count increased by 47.76×10⁹/L (p < 0.0001, 95% CI: 36.81-58.70). The analysis demonstrated progressive recovery, with mean increments of 25.21×10⁹/L, 42.43×10⁹/L, and 64.91×10⁹/L at days 3, 5, and 7, respectively. Efficacy was consistent across all BCLC stages. Notably, multivariate analysis identified a treatment duration of ≥7 days as an independent predictor of ORR (OR = 7.45, 95%CI: 1.95-28.50, p = 0.003). No treatment-related hepatorenal toxicity or thromboembolic events were observed. Conclusions: rhTPO exhibits significant efficacy and a favorable safety profile in managing thrombocytopenia associated with combinatorial interventional therapy with targeted and immunotherapy in HCC. Our data suggest that a minimum treatment duration of 7 days is pivotal for maximizing platelet recovery, thus facilitating treatment continuity.