Synergistic Effects of Romiplostim and Avatrombopag in Severe Chemotherapy-Induced Thrombocytopenia: A Serendipitous Finding.

Chemotherapy-induced thrombocytopenia (CIT) is a severe complication of cancer treatment. Single thrombopoietin receptor agonists (TPO-RAs) often fail in severe/refractory CIT. This study explored the synergistic effect of romiplostim plus avatrombopag for grade 4 CIT.A retrospective analysis was performed on 8 adult patients with nonhematologic malignancies and severe refractory CIT (platelet <25 × 109/L for ≥4 weeks). All received off-label combination therapy (avatrombopag 40 mg/day oral + romiplostim 3 μg/kg/week subcutaneous), with dose titration based on weekly platelet counts. Primary endpoint was platelet ≥100 × 109/L within 8 weeks; safety and chemotherapy resumption were secondary endpoints. Median baseline platelet was 12.5 × 109/L. All eight patients achieved platelet ≥100 × 109/L by week 5 (100% response), with ≥50 × 109/L reached by week 3 for all. No venous thromboembolism, secondary hematologic malignancies, or severe adverse events occurred. Chemotherapy was resumed without CIT-related dose reduction/delay. Romiplostim combined with avatrombopag yields rapid platelet recovery with favorable safety for severe refractory CIT, enabling chemotherapy resumption. It is a promising salvage strategy for single-agent TPO-RA nonresponders, warranting prospective randomized controlled trials for validation.