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Abstract: TH-PO0169

Rare Glomerular Injury After Chimeric Antigen Receptor T Cell Therapy: Collapsing Glomerulopathy and Thrombotic Microangiopathy

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Quiñones-Cruz, Katherine M., The University of Chicago, Chicago, Illinois, United States
  • Song, Ryan M., The University of Chicago, Chicago, Illinois, United States
  • Chang, Anthony, The University of Chicago, Chicago, Illinois, United States
  • Bonilla, Marco, The University of Chicago, Chicago, Illinois, United States
Introduction

Since its emergence, Chimeric antigen receptor (CAR) T-cell therapy has found utility in the management of many hematologic cancers. Cytokine release syndrome (CRS) and immune effector cell (IEC) associated syndromes are known adverse side-effects of CAR T-cell. However, glomerular diseases are rarely seen. We describe a case of biopsy-proven thrombotic microangiopathy (TMA) and collapsing glomerulopathy after CAR T-cell therapy.

Case Description

A 65-year-old male with diabetes mellitus and multiple myeloma initially treated with lenalidomide, bortezomib, and dexamethasone, who achieved very good partial response followed by high dose melphalan and autologous stem cell transplant a year later. He continued maintenance lenalidomide until he was found to have recurrent disease by next-generation sequencing and started on daratumumab and carfilzomib. However, he had progression of disease, and decision was to proceed with CART-ddBCMA with Fludarabine and Cyclophosphamide lymphodepletion. Course complicated by CRS grade 1 (treated with tocilizumab and dexamethasone) and concern for IEC-associated hemophagocytic lymphohistiocytosis (IEC-HS) (treated with Anakinra and Siltuximab). Acute kidney injury (AKI) was noted 6 days after CAR-T therapy with a rise in serum creatinine (sCr) from 0.88mg/dL to 2.12 mg/dL and proteinuria (UPCR 3.52 g/g). A kidney biopsy revealed TMA and collapsing glomerulopathy. He was treated conservatively with diuretics and angiotensin receptor blocker with improvement in proteinuria (1.9 g/g) and return of sCr to 0.98 mg/dL.

Discussion

The incidence of AKI with CAR-T therapy is low, occurring between 8-30%. The etiology of AKI in these patients remains unclear due to lack of histopathological data but it has been attributed to hypotension, vascular permeability causing vasodilatory shock and third spacing leading to intravascular volume depletion. Our case suggests an additional mechanism of kidney injury through direct nephrotoxicity manifesting as collapsing glomerulopathy. Only one other case has been described in literature in which biopsy-proven collapsing glomerulopathy was seen in a patient who developed AKI after CAR T-cell for treatment of acute leukemia and developed complications of CRS and IEC-HS similar to our patient, supporting possibly a shared mechanism of injury to the podocytes.

Digital Object Identifier (DOI)