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Abstract: PO1747

Bintrafusp α-Associated Thrombotic Microangiopathy

Session Information

Category: Trainee Case Report

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Ninan, Jacob, Mayo Clinic, Phoenix, Arizona, United States
  • Reddy, Swetha, Mayo Clinic, Phoenix, Arizona, United States
  • Hommos, Musab S., Mayo Clinic, Phoenix, Arizona, United States
Introduction

Immune check point inhibitors (ICPIs) have been reported to cause acute kidney injury. Acute tubulointerstitial nephritis is the most common finding on renal biopsy. This has resulted in recommendations to forgo renal biopsy in some patients and therapy with empiric steroids. Here we present a different renal pathology related to use of Bintrafusp-α, a novel therapy targeting TGF-beta and PD-L1.

Case Description

A 41 year old man with metastatic cholangiocarcinoma was admitted for hypertension urgency and acute kidney injury following 2 cycles of Bintrafusp-α in 6 weeks. Exam was remarkable for BP 204/101 mmHg, pulse 62/min, muscle wasting and anasarca. His labs revealed hemoglobin 8.9 g/dL, platelets 109 × 109/L, occasional schistocytes, lactate dehydrogenase 626 U/L(112–222 U/L), undetectable haptoglobin, serum creatinine 2.8 mg/dL, microscopic hematuria and protein creatinine ratio 2.79g/g. ADAMTS13 activity 72% (≥70%), antiphospholipid antibody was negative, complement levels normal. The renal biopsy demonstrated acute and subacute thrombotic microangiopathy(TMA). The patient received a dose of Soliris empirically, pending workup for atypical HUS. Further doses of Soliris were held as TMA was attributed to immunotherapy and atypical HUS genetic testing panel returned negative.

Discussion

TMA is characterized by microangiopathic hemolytic anemia and thrombocytopenia. The most studied secondary cause of TMA is drugs. The pathogenesis of drug-mediated TMA is either the generation of an immunologic reaction or its direct dose- and time-dependent toxicity. ICPI monotherapy has a nephrotoxicity incidence of 2-5%. In the largest retrospective study of 1016 patients treated with ICPI therapy, 17% developed AKI, 2% experienced stage 3 AKI and 0.4% required dialysis. TMA was documented in 1 patient receiving Ipilimumab and was HD-dependent. The National Comprehensive Cancer Network guidelines recommend empirically treating AKI in some patients with steroids. We believe renal biopsy is essential, if safe, to rule out causes of AKI that are not remediable with steroids. Renal biopsy would expand our knowledge on the pathology of AKI post-ICPI treatment. We report the first case of TMA associated with the new bifunctional immunotherapy for solid cancers.