Avatrombopag Effectively Maintained Platelet Counts in a Patient with Immune Thrombocytopenia Who Was Intolerant to Tyrosine Kinase Inhibitor Therapy.

BACKGROUND First-line treatments for patients with immune thrombocytopenia include corticosteroids, intravenous immunoglobulin, and anti-D. These may be followed by second- and third-line options, including thrombopoietin receptor agonists and the tyrosine kinase inhibitor fostamatinib. These treatments have different mechanisms and divergent adverse event profiles. We show that fostamatinib-associated adverse events can be mitigated with fostamatinib dose reduction and the introduction of avatrombopag, and that response can be maintained with avatrombopag monotherapy. CASE REPORT A 61-year-old woman with a history of chronic refractory immune thrombocytopenia since 2006 had previously received steroids, rituximab, splenectomy, and eltrombopag without achieving platelet count stability. The patient reported flu-like symptoms in February 2020, with platelet counts ranging from 25×10⁹/L to 50×10⁹/L and isolated occurrences <10×10⁹/L. Platelet counts did not respond to eltrombopag 75 mg/day, 2 courses of rituximab, or multiple courses of prednisone. Within 2 weeks of starting fostamatinib 150 mg twice daily, she reached a platelet count of 523×10⁹/L. She experienced new-onset diarrhea associated with fostamatinib, so the dose was reduced to 75 mg twice daily, and avatrombopag 20 mg/day was added to augment platelet recovery. Platelet levels remained in the supratherapeutic range. She was transitioned to avatrombopag 40 mg/day monotherapy and then 20 mg/day owing to continued supratherapeutic platelet counts. CONCLUSIONS Avatrombopag can be used in combination with fostamatinib to augment platelet response and reduce the severity of adverse events associated with fostamatinib, while maintaining adequate therapeutic response in chronic immune thrombocytopenia. Avatrombopag 40 mg/day monotherapy was quite effective in achieving and maintaining high platelet counts.