Author(s): ,
Alessandro Rambaldi
Bone Marrow Transplant Unit ASST Papa Giovanni XXIII,Bergamo,Italy
Samer Khaled
City of Hope,Duarte,United States
Mark Smith
Canterbury District Health Board - Te Poari Hauora o Waitaha,Christchurch,New Zealand
Marco Zecca
Fondazione IRCCS Policlinico San Matteo,Pavia,Italy
Yok Lam Kwong
University of Hong Kong,Hong Kong,Hong Kong
Kathleen Claes
UZ Leuven,Leuven,Belgium
Nelson Leung
Mayo Clinic,Rochester,United States
Steve Whitaker
Omeros Corporation,Seattle,United States
EHA Learning Center. Rambaldi A. Jun 15, 2018; 215162
Alessandro Rambaldi
Alessandro Rambaldi

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Abstract: PF724

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Thrombotic microangiopathy is a potentially fatal complication of HCT. Mortality greater than 90% has been reported in high-risk cases. HCT-TMA is an endothelial injury syndrome associated with complement pathway activation. Other endothelial injury syndromes include graft versus host disease (GvHD) and diffuse alveolar hemorrhage (DAH). OMS721 is a human monoclonal antibody that inhibits mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway. OMS721 may improve patient outcomes by inhibiting complement-mediated injury during TMA.

This study’s aims were to evaluate the efficacy and safety of OMS721 in patients with HCT-TMA.

OMS721 was evaluated in a 3-stage, uncontrolled Phase 2 study of patients with TMA, including HCT-TMA. Stage 1 evaluated 3 dose levels. One dose level was selected for cohort-expansion Stages 2 and 3. The protocol allowed 4 or 8 once-weekly IV doses of OMS721. Additional ½ doses could be administered to patients who received plasma therapy. HCT-TMA patients had persistent TMA defined as TMA that did not resolve following immunosuppression modification. One patient received OMS721 under compassionate use and received thrice-weekly dosing. A best-matched historical control from the literature was identified for comparison to the outcomes of HCT-TMA patients treated with OMS721. References were chosen to match OMS721-treated patients based on age, allogeneic transplantation, and reports that TMA did not resolve following immunosuppression modification. The references included individual patient survival data and were published in 2000 or later. Kaplan-Meier estimated mean survival was compared between OMS721-treated patients and historical control patients.

A total of 19 patients were included in the analysis, 18 from the study and 1 from compassionate use. Nine OMS721-treated patients died, 4 during study participation. Figure 1 demonstrates a significant increase in median overall survival between OMS721-treated patients and historical controls (347 days vs. 21 days from TMA diagnosis, respectively; Log-Rank p < 0.0001). 

Two patients from this population were previously presented. The compassionate-use patient’s course was complicated by DAH and she did not tolerate previous eculizumab treatment. She responded well to OMS721 and was able to discontinue oxygen therapy, hemodialysis, and platelet transfusions. Another patient had steroid-refractory GvHD post-transplant. He developed TMA with co-existing GvHD and multiple disabling neurological complications. Following OMS721 treatment, his TMA and GvHD resolved, his neurological complications improved, and he was discharged and returned to work.

OMS721 was well tolerated. The most common adverse events were diarrhea and neutropenia. One fatal adverse event of infection-related acute respiratory and renal failure was considered possibly related to OMS721 treatment because the investigator could not definitively rule out possible causation.

In this study, patients with high-risk HCT-TMA had significantly improved overall survival compared to best-matched literature controls. The safety profile was acceptable. This study shows positive outcomes with lectin pathway blockade by MASP-2 inhibition to treat HCT-TMA and other HCT-related complications (i.e., GvHD and DAH) linked to endothelial injury.

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): Stem cell transplant, Thrombotic microangiopathy

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