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Immune checkpoint inhibitors (ICI) are a broad class of immunotherapy drugs used across a wide range of malignancies, but these treatments can also cause autoimmune complications. Minimal change disease (MCD) is rare side effect of ICI therapy and re-challenge of ICI therapy after treatment of MCD has been infrequently reported. We present the first case of successful ICI-rechallenge using low-dose steroid bridging resulting in sustained remission of proteinuria and continued oncologic response.
A 60-year-old Caucasian female with metastatic endometrial cancer presented with a two-week history of weight gain (~10%) and bilateral lower extremity swelling. After progression on carboplatin and paclitaxel, she was subsequently started on pembrolizumab, and demonstrated clinical response after three cycles, the last given 2 weeks before presentation. Her medical history was notable for autoimmune encephalitis previously treated with intravenous immunoglobulin and high-dose steroids prior to ICI therapy.
On examination, she had +3 lower extremity edema. Her labs were notable for hypoalbuminemia (serum albumin: 1.9 g/dL), nephrotic-range proteinuria (10.73 g/d,) and hyperlipidemia (total cholesterol: 461 mg/dL) with normal creatinine levels (0.8 mg/dL). Renal biopsy revealed normal renal histology by light microscopy, but electron microscopy revealed extensive effacement of podocyte foot processes consistent with minimal change nephropathy. Given the temporal association and favorable oncologic response to ICI therapy, the diagnosis of MCD was attributed to pembrolizumab.
ICI therapy was discontinued, and the patient was treated with oral prednisone 60 mg daily (tapered over 24 days) and rituximab (anti-CD20 antibody) 1 g IV given 2 weeks apart. Supportive therapy included bumetanide 1 g IV twice daily, losartan 12.5 mg daily, and atorvastatin 10 mg daily. She achieved complete remission of proteinuria following completion of therapy. Due to her oncologic response to ICI therapy, re-challenge of pembrolizumab was discussed. A bridging dose of prednisone 20 mg for 4 days starting on the day of ICI infusion was recommended to prevent relapse of MCD. Daily weights, urine studies, and basic labs were followed. Three months after ICI re-challenge, the patient remains in renal remission with imaging studies showing sustained cancer response.
MCD secondary to ICI therapy has been previously reported with most cases managed by discontinuing the ICI and tapering corticosteroid over 6 to 24 weeks. Re-challenge with ICI has only been reported in three patients. In two cases, MCD relapsed following ICI re-challenge while in the third case, MCD remission was maintained with daily low-dose prednisone. Here, we report the first successful ICI re-challenge in a patient with ICI-associated MCD using a short course of low-dose prednisone bridging, achieving sustained renal remission and durable anti-tumor response.
