Abstract
To investigate the efficacy of Iptacopan in transplantation-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), we report the case of a 43-year-old male with Acute Myeloid Leukemia, Myelodysplasia-Related (AML-MR, with IDH1 and STAG2 mutations) who developed TA-TMA after allo-HSCT. The patient had an initial partial response to the C5 inhibitor eculizumab, but the disease progressed. Oral Iptacopan (200 mg twice daily) was initiated on Day +36. The patient received a total of six sessions of therapeutic plasma exchange and two concurrent doses of defibrotide during the Iptacopan course. After 30 days of Iptacopan treatment, the patient exhibited a significant hematological response, evidenced by a reduction in LDH (758 U/L to 357 U/L), a rise in platelets (17 to 43×10(9)/L), and a drop in C5b-9 (305.32 to 153.70 ng/mL). This biochemical improvement coincided with key clinical outcomes: resolution of proteinuria and the achievement of sustained red blood cell transfusion independence after day +58 and platelet transfusion independence after day +66, marking a decisive turnaround in his TA-TMA course. Treatment with the novel oral complement inhibitor Iptacopan induced significant hematological and clinical responses in this TA-TMA patient, demonstrating its potential therapeutic efficacy and warranting further clinical investigation.