Pediatric Patient With Severe TA-TMA Elicits Response to Narsoplimab

Supplements And Featured Publications48th Annual Meeting of the EBMT
Volume 01
Issue 01

A pediatric patient with severe transplant-associated thrombotic microangiopathy responded to treatment with narsoplimab after experiencing disease progression on eculizumab.

Michelle L. Schoettler, MD

Michelle L. Schoettler, MD

A pediatric patient with severe transplant-associated thrombotic microangiopathy (TA-TMA) responded to treatment with narsoplimab after experiencing disease progression on eculizumab (Soliris), according to findings presented in a poster during the 48th Annual Meeting of the EBMT.1

“[The infant] developed severe TA-TMA that progressed on adequate blockade of terminal pathway using eculizumab, who had an excellent response to narsoplimab, emphasizing the role of lectin pathway activation in the pathophysiology of TA-TMA,” lead study author Michelle L. Schoettler, MD, an assistant professor in the Department of Pediatrics at Emory University School of Medicine, and coinvestigators wrote in the poster.

TA-TMA–related multi-organ failure is often fatal following treatment with hematopoietic cellular therapy. However, complement and endothelial dysfunction are potentially key disease drivers, even while the lectin pathway’s role in TA-TMA is not well characterized.

MASP-2 is an effector enzyme of the lectin pathway of the complement system, and narsoplimab is a MASP-2 monoclonal antibody. Currently, there is a biologics license application under review with the FDA for use as a potential therapeutic option in adult patients with hematopoietic stem cell transplant–associated TMA.2

In May 2021, the FDA extended the review period following a response from the drug developer, Omeros Corporation, to an information request issued by the regulatory agency. The FDA classified the response as a major amendment, which requires additional time to adequately review. The new action date under the Prescription Drug User Fee Act is October 17, 2021.

Findings of a phase 2 trial (NCT02222545) previously showcased the activity with narsoplimab.3 Here, the agent elicited a complete response rate of 54% (95% CI, 34%-72%) in the total patient population (n = 28). Among 23 patients who received treatment in accordance with study protocol, who had received 4 weeks or more of dosing, the objective response rate with the agent was found to be even higher, at 65% (95% CI, 43%-84%).

However, the efficacy and safety of narsoplimab in pediatric patients have been limited to date. In the analysis presented at the 48th Annual Meeting of the EBMT, investigators evaluated narsoplimab in an infant with refractory TA-TMA that was complicated by diffuse alveolar hemorrhage (DAH).

The patient was a 9-month-old female with KMT2A-MLL leukemia who underwent a 10/10 unrelated bone marrow transplant that was conditioned with busulfan and cyclophosphamide. She experienced veno-occlusive disease, which required ventilator support, renal replacement, and a peritoneal drain.

On day +18, the patient experienced anemia, thrombocytopenia, elevated lactate dehydrogenase, schistocytes, proteinuria, hypertension, and elevated sC5b-9, all of which led to a TA-TMA diagnosis.

Treatment with eculizumab was administered on day +18 and organ function was initially improved and was later extubated and had recovered renal function. However, despite adequate CH50 suppression, the patient developed worsening hematologic markers of TMA and acute respiratory failure on day +34, which required re-intubation. She was diagnosed with DAH and was restarted on CRRT. The patient was also found to have evidence of alternative complement activation with elevated C3a and Bb.

Eculizumab had been discontinued to prevent additional risk of infections, and narsoplimab was then administered at a 4-mg/kg dose intravenously beginning on day +57.

Following narsoplimab for 6 weeks, TA-TMA hematologic markers had improved and the patient was then extubated without any recurrent pulmonary bleeds, CRRT was stopped, and proteinuria improved. To date, narsoplimab is still being administered twice weekly.

The patients’ primary disease relapsed at day +100.

Regarding safety, narsoplimab was found to be well tolerated. Additionally, there was Bb, C3a, C5a, and sC5b-9 normalization plus decreased platelet and hemoglobin transfusion needs. This suggests the rapid reversal of organ dysfunction seen in this patient was likely from lectin pathway blockade, the authors noted.


  1. Schoettler M, Bryson E, Deeb L, et al. Compassionate use of narsoplimab to treat transplant associated thrombotic microangiopathy in a pediatric patient with multi-organ failure. Presented at: 48th Annual Meeting of the EBMT; March 19-23, 2022; virtual. Abstract P377.
  2. Omeros announces extension of FDA review period for narsoplimab in HSCT-TMA. News release. Omeros Corporation. May 20, 2021. Accessed March 22, 2022.
  3. Rambaldi A. Smith M, Whitaker S, et al. Narsoplimab (OMS721) for the treatment of adult hematopoietic stem cell transplant-associated thrombotic microangiopathy. Presented at: 2020 European Hematology Association Congress; June 11-21, 2020; virtual. Abstract S262.
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