Abstract: PUB190
Treatment Dilemma of Malignancy-Associated Nephrotic Syndrome
Session Information
Category: Onconephrology
- 1600 Onconephrology
Authors
- Bohart, Isaac C., Stanford University School of Medicine, Stanford, California, United States
- Lee, Jacqueline, Stanford University School of Medicine, Stanford, California, United States
- Lee, Seolhyun, Stanford University School of Medicine, Stanford, California, United States
Introduction
Nephrotic syndrome can be associated with malignancy. Selecting immunosuppressive therapy for nephrotic syndrome in patients requiring immune checkpoint inhibitors (ICI) poses a unique challenge, in that immunosuppressive therapy may attenuate antitumor efficacy.
Case Description
A 71-year-old woman with hypertension and treated hepatitis C presented with 6 weeks of progressive edema. Serum creatinine was 0.9 mg/dL, serum albumin was 2.4 g/dL (with subsequent worsening to 1.9 g/dL), and urine protein-to-creatinine ratio (UPCR) was 10.3 g/g. Kidney ultrasound incidentally revealed hepatic lesions. Further diagnostic studies confirmed hepatocellular carcinoma with peritoneal carcinomatosis, and a second primary, localized pancreatic adenocarcinoma. Kidney biopsy showed severe foot process effacement without immune-complex deposits, consistent with minimal change disease (MCD). After 2 months of tacrolimus, UPCR remained at 9.0 g/g with a modest improvement in serum albumin (2.7 g/dL) and a substantial reduction in edema.
Discussion
The patient received durvalumab (an anti-PD-L1 agent) and tremelimumab (an anti-CTLA-4 agent) used in combination for the treatment of advanced, unresectable hepatocellular carcinoma. For treatment of MCD, tacrolimus was selected over high-dose glucocorticoids given concerns about attenuating the efficacy of immune checkpoint inhibitors (ICI) for treatment of her malignancy as well as the relatively high likelihood of steroid-resistant or steroid dependent MCD. However, calcineurin inhibitors can also theoretically impair ICI efficacy through T-cell suppression.
Rituximab was also considered as next line therapy given the limited clinical response to tacrolimus. Its selective B-cell depletion spares T cells, the primary effectors of ICI-mediated antitumor activity. Limited clinical data suggest that combining rituximab and ICI preserves antitumor responses. However, rituximab may cause transient T-cell inactivation, and the net effect on ICI therapy remains uncertain.
The patient ultimately opted for comfort-focused care given her poor oncologic prognosis, and a peritoneal drain was placed for refractory ascites requiring weekly paracenteses. She opted to defer further therapy for MCD.
This case highlights the need for close nephrology-oncology collaboration to individualize immunosuppressive therapy in patients requiring ICI treatment.