PB2170 HEPATITIS C VIRUS-DRIVEN MULTIPLE MYELOMA IN STABLE COMPLETE REMISSION AFTER ANTIVIRAL TREATMENT

Abstract

Background: Despite great advances in knowledge and treatment in past decades, multiple myeloma (MM) remains an incurable disease. Several studies suggest its association with infectious pathogens, such as hepatitis C virus (HCV) and Epstein Barr virus (EBV). Aims: In this study, we report on the case of a female MM patient in third relapse (after natural killer (NK) therapy with lenalidomide; bortezomib, lenalidomide, and dexamethasone (BLD); bortezomib, bendamustine, and dexamethasone (BBD) and the antiviral agents sofosbuvir and ledipasvir, who achieved stable complete response (CR) once HCV infection was successfully treated with antivirals, thus establishing a probable relationship between HCV infection and MM in this patient. Methods Serum samples from the patient were analyzed before and after antiviral treatment (Sofusbuvir + Ledipasvir). The HCV burden was determined by RT-qPCR. MRD was evaluated by cytology and MFC immunophenotyping, in bone marrow samples. The number of plasma cell clones and the tumor load were determined in bone marrow samples by next-generation sequencing. The patient's monoclonal immunoglobulin (mc IgG) was isolated by agarose gel electrophoresis and its purity was evaluated by isoelectric focusing. The reactivity to different microbial antigens was determined by means of the multiplex infectious-antigen microarray (MIAA) assay and the commercial kit INNO-LIA HCV score (Fujirebio). Results: The patient, age 59, presented with ISS IIA stage MM (5.7 g/dL mc IgG, 0.27 g/dL free lambda chains, 90% plasma cells in the bone marrow, without cytogenetic alterations, and osteolytic lesions). HCV infection, causing hepatic toxicity, was discovered in this patient before MM disease. The patient was in third relapse of MM treatment when she received anti-HCV treatment. After antiviral therapy, the HCV load in the patient's serum decreased to undetectable levels (Fig. 1A). Simultaneously, the patient achieved CR of MM, with minimal residual disease (MRD) negativity (Fig. 1B). Agarose gel electrophoresis of pre-HCV treatment samples showed one band of mc IgG, which disappeared after anti-HCV treatment (Fig. 1 C). The patient's mc IgG was purified and analysis of its specificity of recognition revealed that it targeted the HCV C1 (core) protein (Fig. 1D). Three years have now passed after HCV treatment, and the patient remains in stable CR of MM.Summary/Conclusion: In this case of refractory MM where the patient's mc IgG targeted HCV, successful HCV eradication with antivirals Sofosbuvir and Ledipasvir resulted in persistent complete remission of MM as well as of hepatitis C. These results suggest that for HCV-positive individuals, a causal relationship exists between HCV infection and the development of MM, and that MM patients infected with HCV benefit from early anti-HCV therapy.