Defitelio (defibrotide)

The patient had an initial partial response to the C5 inhibitor eculizumab, but the disease progressed...The patient received a total of six sessions of therapeutic plasma exchange and two concurrent doses of defibrotide during the Iptacopan course...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.

He was initially diagnosed with sinusoidal obstructive syndrome (SOS) and treated with defibrotide...The patient was initiated on high-dose corticosteroids with rapid clinical and biochemical improvement. This case underscores the diagnostic complexity of HLH, particularly in lymphoma patients undergoing chemotherapy, where overlapping syndromes can delay accurate diagnosis, and highlights the critical importance of early recognition to initiate timely, life-saving immunosuppressive therapy.

P2, N=40, Recruiting, New York Medical College | Trial primary completion date: Dec 2024 --> Dec 2026 | Trial completion date: Dec 2025 --> Dec 2027

She was successfully treated with the urgent insertion of a transjugular intrahepatic portosystemic shunt (TIPS), defibrotide, and high-dose corticosteroids. This case of successful treatment for very severe SOS supports a combination strategy involving the immediate mechanical reduction of portal hypertension through TIPS and drug-mediated inhibition of microvascular thrombosis. Furthermore, this case shows the need for an improved prevention strategy, including the identification of additional risk factors and biomarkers.

P2, N=0, Withdrawn, University of California, San Francisco | N=15 --> 0 | Not yet recruiting --> Withdrawn

P2, N=42, Recruiting, Brigham and Women's Hospital | Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: May 2024 --> Sep 2024

The results from the CECinVOD study collectively confirm the endothelial injury in allo-HCT and in SOS/VOD development, suggesting CECs as a valuable biomarker for its diagnosis and for the identification of patients at higher risk of this complication, especially in cases of late-onset SOS/VOD. Furthermore, CEC kinetics may assist in treatment strategies by providing insights into the optimal timing for discontinuing defibrotide treatment.

P2, N=20, Recruiting, New York Medical College | Initiation date: Dec 2023 --> Mar 2024 | Not yet recruiting --> Recruiting

P2, N=15, Not yet recruiting, University of California, San Francisco

P2, N=20, Not yet recruiting, New York Medical College | Initiation date: Aug 2023 --> Dec 2023

P2, N=20, Completed, New York Medical College | Active, not recruiting --> Completed | Trial completion date: Jul 2023 --> Nov 2023

One study reported outcomes for 206 children who received supportive care for VOD/SOS during 6-thioguanine therapy for ALL; only three pts had acute hepatic failure and all pts recovered from VOD/SOS. Non-HCT VOD/SOS occurs in diverse disease areas, including hematologic and solid tumor cancers. A lack of consensus regarding VOD/SOS diagnosis in the non-HCT setting may lead to underdiagnosis; therefore, clinicians should be vigilant for VOD/SOS even in non-HCT pts. Though defibrotide is approved for post-HCT VOD/SOS, there is no approved therapy for non-HCT VOD/SOS; future trials should focus on diagnosis and treatment outside the HCT setting, which represents a significant unmet need.