Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies and Myeloma

Abstract

Background: Multiple myeloma remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Methods: We studied thirteen patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma with previous HCV infection. Viral load was quantified using the VERIS MDx system. The antigen specificity of purified monoclonal immunoglobulins was determined using the INNO-LIA HCV Score, dot-blot assays, and a multiplex infectious-antigen microarray. Findings: The target of the purified monoclonal immunoglobulin was identified for 8/13 patients. The monoclonal immunoglobulin from 6/8 patients reacted against HCV. Four of the patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with multiple myeloma in third relapse achieved complete remission with minimal residual disease negativity, as assessed by next generation multiparameter flow cytometry. Two patients did not receive antiviral treatment and progressed. For the two additional patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or multiple myeloma disease. Interpretation: Our results suggest a causal relationship between HCV infection and MGUS and multiple myeloma progression. When HCV is eliminated, chronic antigen-stimulation disappears, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and multiple myeloma. Funding Statement: This work was supported by grants to S.H. from the Ligue Nationale contre le Cancer (Comites Departementaux 44, 56, 29, 85, 35) and International Myeloma Foundation (IMF) (Brian D. Novis senior grant). We acknowledge of Instituto de Investigacion Hospital 12 de Octubre (i+12), CIBERONC, AECC (Accelerator Award), and the CRIS foundation for their help. M.L. had a postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness (FPDI-2013-16409) and a grant from the Spanish Society of Hematology Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by our Institutional Review Board and the patients provided written informed consent in accordance with the Declaration of Helsinki.