Outcomes of HCV-Positive Patients with Lymphoma Treated with Rituximab-Containing Therapies

Introduction: The impact that hepatitis C virus (HCV) infection has on the clinical outcome of patients with lymphoma treated with rituximab-containing therapies is uncertain. Rituximab has improved outcomes in patients with aggressive lymphomas however the prognostic value of rituximab in HCV infected patients has not been well established. It has been shown that reactivation is a common complication in patients with hepatitis B treated with rituximab. It is possible that patients with hepatitis C also develop reactivation with rituximab resulting in worsening liver function and a poor clinical outcome. A prior Japanese study showed that HCV-positive patients with diffuse large B-cell lymphoma have a high incidence of severe hepatic toxicity (Ennishi, D., Maeda, Y., et al. 2010). In this study we wanted to further analyze this idea and see if it is applicable to American population with hepatitis C and lymphoma receiving rituximab-containing therapies.

Methods: We collected data from patients who were HCV-positive with lymphoma treated with rituximab between 2003 and 2014 at Montefiore Medical Center. Patients were included who were over 18 years old with a positive HCV test prior to treatment. Data was analyzed using statistical software Stata (version 12.0, StataCorp LP, College Station, TX, USA).

Results: A total of 33 HCV-positive patients with lymphoma were included. Most of these patients (82%) had diffuse large B-cell lymphoma (DLBCL). Of the 33 patients, 24 (73%) showed worsening liver function after starting Rituximab containing therapy. Hepatitis C viral load before and after the treatment was documented for 8 patients. 5 of these 8 patients had clear reactivation of hepatitis C with rising hepatitis C viral load. All of these 5 patients noted with worsening of liver function tests. These patients received an average of 2 doses of Rituximab before having the rise in liver function tests (LFTs). Also, the median duration to see a rise in liver transaminases was at 2.5 months with the peak level in liver enzymes observed at 4 months after starting rituximab.

Conclusion: These results show that patients with HCV infection have a high incidence of hepatic toxicity with rituximab. Some of these patients also showed evidence of reactivation with increased hepatitis C viral load. Further studies need to be done to determine if addition of new oral hepatitis C treatments like Sofosbuvir to the chemotherapy would change the course of viral reactivation and hepatic toxicity. These patients may need closer hepatic monitoring during and after treatment with rituximab.

References:

Ennishi, D., Maeda, Y., et al. (2010). “Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis.” Blood 116(24): 5119-25