Abstract: SA-PO218
An Unusual Case of Steroid Refractory Allergic Interstitial Nephritis Related to Prior Ifosfamide Exposure
Session Information
- Onconephrology: Kidney Outcomes during Cancer Treatment and Nephropathies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Sardar, Sundus, Penn State College of Medicine, Hershey, Pennsylvania, United States
- Matarneh, Ahmad, Penn State College of Medicine, Hershey, Pennsylvania, United States
- Gutgarts, Victoria, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Trivedi, Naman, Penn State College of Medicine, Hershey, Pennsylvania, United States
- Ghahramani, Nasrollah, Penn State College of Medicine, Hershey, Pennsylvania, United States
Introduction
Tazemetostat, an EZH2 inhibitor, recently approved for treating solid and hematologic malignancies. EZH2 overexpression and mutations drive tumor growth. While Tazemetostat's side effects have been studied, further investigation is needed to establish their incidence. Reports suggest Tazemetostat can activate the innate immune response with T-cells against an antigen, which could be a medication, infection or an unknown factor. Our case report discusses allergic interstitial nephritis (AIN) presumed to be induced by Tazemetostat in the context of ifosfamide use.
Case Description
A 43-year-old male with metastatic epithelioid sarcoma was initially treated with ifosfamide and doxorubicin, developing Fanconi syndrome from ifosfamide toxicity. Tazemetostat was later initiated as secondary treatment. After 8 months, his renal function deteriorated, with creatinine increasing from 0.8mg/dL to 2.04mg/dL and proteinuria reaching 3.25 g/24h. Tests showed a normal blood count, negative (ANA, ANCA), normal complement levels, but positive PR3-ANCA antibodies. A kidney biopsy confirmed tubulointerstitial nephritis. Despite 6 weeks of oral steroids (60mg daily), renal function did not improve. Mycophenolate (MMF)was introduced for steroid-refractory AIN, but he developed anemia requiring blood transfusion, leading to a dose reduction. Renal function continued to decline, reaching 3.4mg/dL. A second kidney biopsy revealed severe tubulointerstitial nephritis with focal necrosis, suggesting ifosfamide-induced nephropathy. Imaging showed new inguinal lymph node enlargement, under evaluation. MMF is being tapered until biopsy result.
Discussion
Tazemetostat is a novel anticancer agent. Known side effects include nausea, headache, abdominal pain, and increased risks of T-cell lymphoma and myelodysplastic syndrome. No established link between Tazemetostat and AIN exists, necessitating further research. Studies suggest Tazemetostat may trigger an innate T-cell response to an antigen, potentially causing allergic interstitial nephritis. In our patient, we speculate ifosfamide acted as an antigen, triggering an immune response. AIN management involves discontinuing the offending agent and using immunosuppressants like steroids and MMF. Further research is needed to refine Tazemetostat's safety profile and optimize management strategies.