Two cases of delayed onset of immune-related adverse events after discontinuation of nivolumab in patients with metastatic renal cell cancer

Abstract

Introduction: Delayed onset of immune-related adverse events following immune-checkpoint inhibitor discontinuation is underrecognized because of little available evidence.

Case presentation: A 50-year-old man with metastatic renal cell carcinoma (Case 1) and 58-year-old woman with renal cell carcinoma and retroperitoneal lymph node metastasis (Case 2) underwent nivolumab therapy. Case 1: Progressive disease forced nivolumab discontinuance after 18 months, and he underwent two courses of tyrosine kinase inhibitor therapy. immune-related adverse events of pneumonitis, hepatitis, and renal dysfunction were diagnosed 142 days after nivolumab discontinuation, and he recovered with immunosuppressive treatment. Case 2: The immune-related adverse event of pneumonitis forced nivolumab discontinuance after 14 months, and two courses of tyrosine kinase inhibitor therapy were administered. The immune-related adverse event of hepatitis was diagnosed 436 days after nivolumab discontinuation, and she recovered with immunosuppressive treatment.

Conclusion: Two patients with delayed onset of immune-related adverse events after nivolumab discontinuation were recovered with immunosuppressive treatment.

Keywords: delayed onset; immune‐checkpoint inhibitor; immune‐related adverse events; renal cell carcinoma.

Fig. 1

Time course of CT imaging, immunosuppressive therapy, and changes in serum levels of ALT and Cr. (a) Chest CT on day 124 after discontinuation of nivolumab. Slight but diffuse ground‐glass opacities in the bilateral lungs were observed. (b) Chest CT on day 142 after discontinuation of nivolumab. Worsening of ground‐glass opacities in the bilateral lung was observed. (c) Time course of immunosuppressive therapy and changes in serum levels of ALT and Cr. mPSL was started 142 days after discontinuation of nivolumab. After 3 doses of pulse corticosteroid therapy with 500 mg mPSL, PSL (1 mg/kg) was administered with MMF. (d) Chest CT at 43 days after initiation of pulse corticosteroid therapy showed improvement of ground‐glass opacities.

Fig. 2

Time course of immunosuppressive therapy and changes in serum levels of ALT, γGTP, and t‐bil. ALT was increased to 535 IU/L (CTCAE grade 3) 425 days after discontinuation of nivolumab. Although ALT decreased to 205 IU/L (CTCAE grade 2) after discontinuation of Paz, serum levels of γGTP and t‐bil increased to 1490 IU/L (CTCAE grade 4) and 15.8 mg/dL (CTCAE grade 4), respectively. mPSL was started 436 days after discontinuation of nivolumab. After three doses of pulse corticosteroid therapy with 1000 mg mPSL, PSL (2 mg/kg) was administered with MMF.