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Kidney Week

Abstract: SA-PO0662

Ravulizumab Treatment in Pediatric Patients with Hematopoietic Stem-Cell Transplantation-Associated Thrombotic Microangiopathy Is Associated with Lower Rates of Hypertension, Proteinuria Reduction, and High Survival

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Schoettler, Michelle L, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States
  • Bueno, David, Pediatric Hematology and Oncology Department, La Paz University Hospital, Madrid, Spain
  • Krauss, Aviva, Department of Hematology-Oncology, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
  • Chaudhury, Sonali, Stem Cell Transplantation and Cellular Therapies, Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Bachman, Eric S., Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
  • Liu, Peng, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
  • Fry, Jude, Alexion, AstraZeneca Rare Disease, Baar, Switzerland
  • Williams, Cory, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
  • Singh, Ajay K., Brigham and Women’s Hospital, Boston, Massachusetts, United States
  • Locatelli, Franco, Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital and Catholic University of the Sacred Heart, Rome, Italy
  • Takahashi, Yoshiyuki, Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Dvorak, Christopher, Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, San Francisco, California, United States
  • Lawson, Sarah, Department of Oncology & Hematology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, United Kingdom
Background

Thrombotic microangiopathy after hematopoietic stem cell transplant (HSCT-TMA) is a life-threatening condition driven by endothelial damage and terminal complement dysregulation. Kidney manifestations are common, and acute kidney injury and proteinuria (random urine protein/creatinine ratio [rUPCR]) ≥1 mg/mg are high-risk features. Early intervention is critical to limit kidney damage and increase survival.

Methods

This phase 3, multicenter, open-label, single-arm trial (ALXN1210-TMA-314; NCT04557735) enrolled pediatric patients with high-risk HSCT-TMA. Participants aged <18 years with a diagnosis of TMA within 12 months of HSCT received weight-based intravenous ravulizumab and best supportive care for 26 weeks. Inclusion criteria included rUPCR ≥1 mg/mg.

Results

41 participants (median age, 6.0 years) were enrolled; 28 completed the 26-week treatment period. At baseline, median (range) proteinuria was markedly elevated at 2.5 (0.2-29.9) mg/mg; median (range) eGFR was 114.1 (17.0-304.0) mL/min/1.73m2; and 78.0% of participants (32/41) were treated with antihypertensives (53.7% [22/41] reported hypertension as an organ dysfunction [OD] cardiopulmonary symptom). At week 26, median (range) proteinuria decreased to 0.4 (0.1-5.3) mg/mg. There was no significant change in median eGFR, but OD related hypertension decreased to 20.0% (6/30) of evaluable patients. Overall survival at week 26 was 87.2% (36/41; 95% CI, 71.8-94.5). There were no unexpected safety findings.

Conclusion

In pediatric patients with high-risk HSCT-TMA, ravulizumab treatment was associated with clinically meaningful improvements in proteinuria and hypertension, as well as high survival at 26 weeks.

Funding

  • Commercial Support – Alexion, AstraZeneca Rare Disease

Digital Object Identifier (DOI)