Direct-Acting Antivirals Induce Lymphoproliferative Disease Response in HCV-Infected Patients With Indolent B-Cell Non-Hodgkin’s Lymphoma: A Prospective Observational Study

B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients. We enrolled patients seen at our center during 2014–2021; we analyzed only chemotherapy-naïve patients treated with DAAs. Patients who required immediate conventional treatment for lymphoma were excluded from the study. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and lymphoproliferative disease response, classified as complete response, partial response, stable disease, or progressive disease. The secondary endpoints were overall response rate (ORR) of NHL, duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Nine patients met the study criteria and were analyzed. Most patients were male (n = 6), White (n = 6), younger than 65 years (n = 6), and non-cirrhotic (n = 8); had HCV genotype 1 (n = 5); and had been infected for more than 30 years (n = 7). All patients achieved SVR12. Six patients (67%) had complete response, and 3 (33%) had progressive disease. The ORR was 67%. The median DOR was 51 months (range 16–81 months). The 5-year DOR, OS, and PFS rates were 100%, 83%, and 67%, respectively. HCV-associated NHL is a late extrahepatic complication of HCV. Infected patients with indolent NHL have an excellent virologic responses to DAAs and most of them experienced a favorable oncologic response after HCV eradication without chemotherapy.