387 - Early Results of Phase II Study Using OMS721 in Patients with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HCT-TMA)

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Introduction: TMA is a potentially life-threatening complication of HCT currently managed largely by amelioration of inciting factors including avoidance of calcineurininhibitors and treatment of ongoing infections, as well as supportive measures such as hemodialysis. Patients who do not respond have poor prognosis. Plasma exchange has not shown efficacy and no other therapy is approved. Complement activation has been reported in the pathogenesis of HCT-TMA. OMS721 is a human monoclonal IgG4 inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement activation. Here we report early results of OMS721 treatment in HCT-TMA patients. Methods: This is a Phase 2 uncontrolled, open-label, 3-stage study of OMS721 to assess safety, tolerability and clinical activity of OMS721 in patients with TMA (HCT-TMA, aHUS and TTP). Stage 1 included dose-escalation cohorts, Stage 2 expands disease-specific cohorts and Stage 3 provides optional extended treatment. For inclusion, patients with HCT-TMA should demonstrate thrombocytopenia and evidence of microangiopathic hemolytic anemia, and at least 2 weeks must have elapsed since changes in immunosuppressive treatment. HCT-TMA patients received OMS721 X *Dose is confidential.*Dose is confidential. mg/kg IV once weekly (Stage 1 up to 4 weeks and Stages 2 and 3 up to 8 weeks). Patients could receive additional half doses if given plasma therapy. Results: 5 HCT-TMA patients were enrolled; 2 patients entered Stage 1 and 3 patients entered Stages 2 and 3. All patients were adults and received HCT for hematological malignancies. Figure 1, Figure 2, Figure 3 provide the change from baseline in TMA variables. These figures provide data on all 5 patients, two of whom discontinued the study (1 each in Stage 1 and Stage 2, both after 2-3 weeks) with one subsequently relapsing and the other receiving palliative care.Figure 2LDH change from baseline over time.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Change in haptoglobin over time.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Statistically significant improvement in LDH and haptoglobin were observed during treatment. Platelet count improved but did not reach statistical significance in this small number of patients. Of the 3 patients who completed treatment, 1 did not show improvement in creatinine but was receiving concomitant nephrotoxic agents; RRT was not required. Creatinine improved or remained normal in the other 2 patients. On extended follow up, 1 patient experienced graft failure and is awaiting a second transplant. The other 2 patients remain stable. OMS721 treatment was well tolerated with no safety concerns. Conclusions: OMS721 improved TMA markers in HCT patients who had not responded to conservative measures. No toxicity signals were observed during treatment. By inhibiting the lectin pathway, OMS721 may be beneficial in the treatment of HCT-TMA and further study is ongoing.