Abstract: SA-PO0772
Collapsing Glomerulopathy After Chimeric Antigen Receptor T-Cell Therapy for Relapsed Multiple Myeloma
Session Information
- Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Valenzuela, Diego Alfonso, The University of Chicago Medicine, Chicago, Illinois, United States
- Cullen, Ryan, Endeavor Health, Evanston, Illinois, United States
- Henriksen, Kammi J., The University of Chicago Department of Pathology, Chicago, Illinois, United States
- Ho, L. Tammy, Endeavor Health, Evanston, Illinois, United States
Group or Team Name
- University of Chicago Section of Nephrology
Introduction
B-cell maturation antigen (BCMA) Chimeric antigen receptor T-cell (CAR-T) therapy uses the native immune response to treat refractory hematologic cancers. Acute kidney injury (AKI) is a known effect of CAR-T, and it is attributed to an immunologic response coined Cytokine Release Syndrome (CRS). Biopsy-proven glomerular disease after CAR-T is rare. We report a case of biopsy-proven post-CAR-T collapsing focal segmental glomerulosclerosis (FSGS).
Case Description
63-year-old male with IgG lambda multiple myeloma underwent multiple lines of therapy for relapsed disease, including autologous stem-cell transplant. After years of treatment, the patient received ciltacabtagene autoleucel BCMA CAR-T. On days 6 and 7 post infusion, the patient developed CRS Grades 1 and 2, respectively, treated with three doses of tocilizumab and dexamethasone and returned to CRS Grade 0 by day 8. AKI was initially noted at this time as serum creatinine (sCr) peaked at 1.8-mg/dL; it returned to the patient's baseline of 1.4-mg/dL by day 11. On day 15, 4 days after the initial AKI resolved, the patient developed a second AKI (sCr peak of 3.90-mg/dL), acute anasarca, and severe nephrotic syndrome (UPCR peak 46-g/g; confirmed with 24-hour collection). Kidney biopsy noted early FSGS with collapsing features and severe podocytopathy. He was managed supportively with anti-proteinurics and diuretics leading to improved proteinuria (2.1-g/g) and renal function (sCr 1.5-mg/dL) on discharge.
Discussion
AKI is not uncommon with CAR-T; proposed AKI mechanisms following CRS suggest that high levels of pro-inflammatory cytokines like interleukin 6, interferon-gamma, tumor necrosis factor alpha, and granulocyte colony stimulator factor, released directly by the CAR-T cells, lead to increased vascular permeability and leakage, resulting in third-spacing and intravascular volume depletion. Cytokines can also directly alter the glomerular basement membrane's negative charge and can induce podocyte death and permeability. Animal models have shown IL-6 expression in inflamed glomeruli. BCMA CAR-T may also target kidney-dwelling plasma cells leading to cytokine release and podocytopathy. Given our biopsy findings and the unique timing of nephrotic syndrome, it is plausible that a novel mechanism of kidney damage following CAR-T, in addition to CRS, may lead to podocytopathy.