Safe and effective treatment of follicular lymphoma in patients with HCV‐infection

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Numerous studies have found a high prevalence (13%-18%) of HCV infection in patients with non-Hodgkin B-cell lymphomas (NHLs). Some studies indicate that prevalence of HCV infections in follicular lymphoma (FL) patients is not different from those in the population. Novel highly potent direct-acting antivirals (DAAs) associated with high rate of cure (>95%) in chronic HCV infection patients. The last European Association for Study of Liver (EASL) guidelines recommends treatment of HCV-associated lymphoma with DAAs in combination with specific chemotherapy, but taking into consideration potential drugdrug interactions which should be monitored and adjusted accordingly during treatment. Little is known about the efficacy and safety of treatment in these patients, especially in those with concurrent administration of immunochemotherapy (I-CT). FL chemotherapy is associated with the risk of complications. The aim of our retrospective comparative study was to evaluate efficacy, safety and impact to the outcome of HCVpositive FL patients treated with DAAs concurrently with a I-CT seen at our institution during 2010-2019. The overall prevalence of HCV infection in FL patients (cases) was 3.1% (11 out of 360). Cases were matched with 105 HCV-negative FL patients who had similar clinical characteristics and had undergone similar I-CT (comparison group). Cases and comparison group were observed for median 32 and 53 months, respectively, after the start of the first I-CT. Statistical analysis was performed using Kaplan-Mayer estimates. Baseline clinical and histological features of patients with FL are summarized in Table 1. In all cases antiviral therapy was started 5 days before I-CT and lasted a total of 12 weeks in parallel with I-CT. Patients with liver cirrhosis and genotype 3 HCV additionally received ribavirin according to EASL guidelines. The rapid on-treatment (during first 4 weeks) and end of treatment response (serum HCVRNA negativity and normalization of alanine aminotransferase) were achieved in 10 (91%) and 11 (100%) cases, respectively. The overall sustained virologic response rate (undetectable HCVRNA 12 weeks after treatment discontinuation) was 82% (9/11), and 2 virologic failure (relapse) reported at 12 weeks post-treatment in cirrhotic patients infected with HCV genotype 1 and 3 who were received sofosbuvir plus daclatasvir. In both relapsed patient genotypic drug-resistance analysis performed after failure revealed Y93H resistance-associated substitutions in non-structural 5A region of HCV, associated with a low treatment response. First patient (with genotype 1 HCV) thereafter successfully retreated with new DAA regimens (sofosbuvir/velpatasvir and RBV plus asunaprevir during 12 weeks). Second patient afterwards died due to progression of FL. Both patients with HBV coinfection received entecavir for HBV reactivation prophylaxis. All HCV-infected patients received as first-line therapy rituximab, doxorubicin, cyclophosphamide, vincristine and prednisone (R-CHOP) and thereafter rituximab maintenance for up 2 years. Four (36.5%) patients experienced I-CT-induced mild hepatic toxicity (grade 1 alanine aminotransferase increase) without I-CT interruption or discontinuation. No clinically significant drug-drug interactions between I-CT and DAAs were developed. Overall, 9 out of 11 patients obtained complete remission after I-CT, whereas disease progression (after 3 and 21 months from the start of treatment) and death (after 8 and 54 months from the start of treatment) occurred in 2 patients (one of them with HCV infection relapse). The 3-year overall survival (OS) and