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Kidney Week

Abstract: PO2209

Narsoplimab, Another Tool in the Management of Thrombotic Microangiopathy in Stem Cell Transplant Recipients

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Report

  • 1500 Onco-Nephrology

Authors

  • Mamlouk, Omar, Section of Nephrology, MD Anderson Cancer Center, Houston, Texas, United States
  • Ahmed, Ali A., Division of Renal Diseases and Hypertension, University of Texas Health Science Center at Houston- McGovern Medical School, Houston, Texas, United States
  • Coke, Howard H., Division of Renal Diseases and Hypertension, University of Texas Health Science Center at Houston- McGovern Medical School, Houston, Texas, United States
  • Mandayam, Sreedhar A., Section of Nephrology, MD Anderson Cancer Center, Houston, Texas, United States
Introduction

Thrombotic microangiopathy (TMA) is a severe complication in recipients of hematopoietic stem cell transplants (HSCT). Its treatment remains controversial due to its complex and not fully understood mechanism. As more emerging evidence supports the role of complement dysregulation in the observed endothelial injury, anti-complement medications have emerged as a potential therapy. Narsoplimab is an anti-complement therapy that was granted FDA designations for HSCT-TMA as a breakthrough therapy. We hereby report the first case of Narsoplimab use in a HSCT adult recipient with TMA in the United states.

Case Description

A Caucasian women in her early 70s with medical history of relapsed B- cell acute lymphocytic leukemia post allogenic HSCT who was treated with Venetoclax and MiniCVD regimen with a hospital course significant for E. coli bacteremia, CMV pneumonia and acute kidney injury. Creatinine rose from 1.6 to 3.3 mg/dl, over 2-weeks, despite the discontinuation of tacrolimus and treating the sepsis. Urinalysis was significant for pyuria, hematuria, granular casts and +1 proteinuria. She had elevated C5b9 and LDH levels (363 ng/ml and 326 U/L respectively) with schistocytes noted in blood smear, suggestive of TMA. Renal biopsy was significant for ATN and acute TMA, for which we decided to treat her with anticomplement therapy with Narsoplimab. She received twice weekly doses for 4 weeks and had significant improvement in renal function (Cr improved to 0.8 mg/dl), however she developed worsening respiratory status secondary to possible diffuse alveolar hemorrhage and family withdrew care in week 4 of therapy.

Discussion

Narsoplimab is a human monoclonal antibody that inhibits mannan-binding lectin associated serine protease-2 (MASP-2) which is an essential enzyme in the complement system lectin pathway. It is designed to prevent endothelial injury without interfering with other complement pathway roles. Data from phase 2 study showed an improvement in patient survival and TMA blood markers (LDH, haptoglobin, and platelet count). It might improve renal function as well as its inhibition to lectin activation pathway can ameliorates proteinuria induced kidney injury. However she didnot have improvement in her platelet count, LDH and C5b9 levels. Further studies are ongoing (Phase 3 trials in IgA nephropathy and HSCT-TMA) to evaluate such renal benefits.