Nivolumab rechallenge after severe immune hepatitis in a metastatic renal cell cancer patient with hepatitis B and no detectable primary

Demir L., CANAZ F.

Indian Journal of Cancer, vol.60, no.1, pp.114-120, 2023 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.4103/ijc.ijc_23_21
  • Journal Name: Indian Journal of Cancer
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.114-120
  • Keywords: HBV positive, immune hepatitis, metastatic RCC without primary, nivolumab, rechallenge
  • Eskisehir Osmangazi University Affiliated: Yes


Renal cell carcinoma (RCC) is an aggressive tumor with high metastatic potential and most of cases are determined incidentally on radiologic imaging. Metastatic RCC (mRCC) without a primary is very rare, and only a small number of cases have been reported in the literature. In recent years, immune checkpoint inhibitors have been used to treat mRCC, but they are associated with immune-related adverse events. Immune hepatitis is rare and usually observed within three months of initiation of therapy. Patients with hepatitis B virus (HBV) infection have generally been excluded from immunotherapy trials, although a small number of reports and retrospective studies exist on the use of immunotherapy in patients with HBV infection. A 59-year-old man was diagnosed with mRCC with adrenal and liver metastases and vena cava inferior thrombosis but without evidence of a primary. Second-line therapy with nivolumab achieved a good clinical response, but grade IV immune-related hepatitis was observed after one year. He also had an occult HBV infection. However, HBV reactivation did not occur with continuous entecavir prophylaxis. The hepatitis gradually resolved within two months without any management, and the patient was rechallenged with nivolumab. Metastatic RCC rarely presents without a primary mass in the kidney. In such cases, histologic and immunohistochemical characteristics are critical. Nivolumab-induced immune hepatitis may occur as late as one year after initiation of therapy. Rechallenge of immunotherapy may be considered in selected patients. HBV infection is not a contraindication for immunotherapy, these patients can be treated safely with frequent monitoring and antiviral prophylaxis.