Salvage Therapy in Cancer Patients With Hepatitis C Infection Failing Direct-Acting Antivirals: A Prospective Study

Background Direct-acting antivirals (DAAs) are commonly used in Hepatitis C (HCV)-infected cancer patients. While treatment failure in these patients is rare, little information exists regarding antiviral salvage therapy. We evaluated the treatment outcomes of this patient population. Methods Cancer patients who received initial DAAs (01/2014-06/2016) were analyzed for viral relapse, defined as reappearance of HCV RNA in serum after discontinuation of DAAs. We evaluated safety and efficacy of salvage. RAS (resistance-associated substitutions) to NS5A/B and NS3 were identified using commercially available assays (population sequencing). Results Of 160 patients enrolled in a prospective observational study, 15 (15/160; 9%) experienced treatment failure. Of these, 7 received salvage therapy (7/15; 47%) (Table). The majority of patients were men (86%), cirrhotics (57%), and had solid tumors (71%). Ultimately 3/7 (43%) patients achieved sustained virologic response (SVR). Of the 4 patients who failed first salvage treatment, 3 (75%) had RASs prior to such therapy, 3 (75%) had HCC, and 1 (25%) underwent second salvage. None of the patients experienced grade 3/4 adverse events. Conclusion HCV relapse after DAAs is rare in cancer patients, but the efficacy of salvage is suboptimal. More effective rescue therapies are needed. Disclosures All authors: No reported disclosures. Table: Patient characteristics, DAA regimens, and outcomes Gender Age Genotype Cirrhosis Malignancy IFN experienced DAA regimen failed Duration (weeks) NS3 RAS at failure NS5A/B RAS at failure First salvage DAA Duration (weeks) Adverse Events Grade 3 or 4 Virologic outcome M 56 1a Yes Colon Yes SOF/IFN/RBV 12 No No SOF/LDV 24 No SVR24 M 87 1b Yes HCC No SOF/SIM 12 No No SOF/LDV/RBV 24 No Relapse M 65 1a Yes DLBCL, HCC No SOF/LDV 12 No Q30R SOF/SIM/RBV 24 No Relapse F 56 3a No DLBCL Yes SOF/RBV 24 No No SOF/DCV/RBV 24 No SVR24 M 58 1a No HCC No SOF/LDV 12 No Q30Q/H, Y93H SOF/SIM/RBV 24 No SVR24 M 63 1a Yes HCC Yes SOF/LDV 24 No Q30R SOF/VEL/RBV 24 No Relapse M 66 1a No SCC No SOF/LD 12 Q80K, D168E M38A, Q30H ELB/GZV/RBV 24 No Relapse DCV, daclatasvir; DLBCL, diffuse large B-cell lymphoma; ELB, elbasvir; GZV, grazoprevir; HCC; hepatocellular carcinoma; LDV, ledipasvir; RBV, ribavirin; SCC, squamous cell carcinoma; SIM, simeprevir; SOF, sofosbuvir; SVR24, SVR at 24 weeks.