Virologic Clearance of Hepatitis C Is Associated with Improved Outcomes in African American Patients with Lymphoma

Background: Association of hepatitis C virus (HCV) infection and B-cell non-Hodgkin Lymphoma (B-NHL) is well-established. Directly-acting antiviral HCV therapy (DAA) results in very high rates of sustained viral response (SVR) and HCV cure. Studies of the impact of successful antiviral therapy on lymphoma outcomes in HCV-infected patients can have important implications for patient management and for understanding of the biology of different lymphomas. The strongest evidence of positive impact of HCV antiviral therapy on lymphoma regression is available for indolent lymphomas, especially marginal zone lymphoma. Impact of antiviral therapy on HCV-associated aggressive B-NHL is still under investigation. Furthermore, there is no data on outcomes for HCV-associated B-NHL in African-American (AA) patients. The aim of this study was to evaluate lymphoma characteristics and outcomes in HCV-associated B-NHL, in a predominantly AA population.

Methods: All consecutive patients with lymphoma and reactive HCV Antibody (HCV Ab+) diagnosed and treated at our center between January 2003 and December 2017 were studied. Patients with HCV-associated mixed cryoglobulinemia without any overt lymphoma, HCV-associated paraproteinemia and patients who did not have antiviral treatment history available were excluded. All information was obtained by review of electronic medical records. Baseline patient characteristics including age, sex, race, comorbidity including HIV infection, lymphoma stage, histology, prognostic score and baseline lactate dehydrogenase (LDH) were recorded. Lymphomas were classified according to the 2016 WHO classification. Prognostic score was calculated using International Prognostic Index (IPI) for aggressive lymphomas, Follicular Lymphoma International Prognostic Index (FLIPI) for indolent lymphomas other than chronic lymphocytic leukemia (CLL) and CLL-IPI for CLL. Details of lymphoma treatment and antiviral therapy were recorded. Virologic clearance (VC) was used to collectively describe both SVR (undetectable HCV RNA 12 weeks after completion of antiviral treatment) and spontaneous clearance of HCV without treatment. Study outcomes were overall response rate (ORR), complete response rate (CR), overall survival (OS) and progression free survival (PFS).

Results: We found 397 patients with lymphoma at our institution, of which, 40 patients had HCV. Thirty-eight patients had complete lymphoma and antiviral treatment history available and were included in the analysis. Median age was 58 years, 90% were AA; 68% were men. Diffuse large B-cell lymphoma (DLBCL) was the predominant histology (50%). Advanced stage (64%), aggressive lymphoma (60%), good prognostic score (74%) and elevated LDH (66%) were common. A total of 21 patients were treated, 18 with DAA and 3 with interferon-based therapy. Twenty-two patients had VC, either spontaneous or with antiviral therapy. Patients with VC, had significantly higher ORR (95% vs 69%, RR 2.4, CI₉₅ 1.3-4.4, p<0.05) and CR (73% vs 38%, 2.29, CI₉₅ 1.1-5.0.0, p<0.05) compared to patients without VC. Median OS was also significantly higher in patients with VC than patients without VC (not reached vs 89 months, RR 0.4, CI₉₅ 0.2-0.6, p<0.05) . Median PFS was not significantly different between two groups. We analyzed ORR and CR in subgroups of aggressive lymphoma, indolent lymphoma and DLBCL. Patients with VC had significantly higher CR then patients without VC in the subgroups of aggressive lymphoma and DLBCL (100% vs 46% and 100% vs 45% respectively, p<0.05), while ORR was not different.

Conclusions: Hepatitis C VC is associated with improved CR and OS in predominantly AA lymphoma patients including patients with aggressive B-NHL. The precise role and timing of HCV antiviral therapy in HCV-associated aggressive B-NHL should be assessed in large prospective studies that include AA patients.