Multiple Myeloma in Patients with HCV-Related Disease:a Case Report
Authors: Vincelli Iolanda D. , Cufari Patrizia , Di Raimondo Francesco , Massimo Martino , Gentile Massimo , Morabito Fortunato , Ciolli Stefania , Rossi Marco , Ronco Francesca 
Published: November 2019

Abstract
Hepatitis C virus (HCV) is a global health infection that affects about 170 million persons worldwide an it is the principal cause of chronic live-diseases. Progression to chronic disease occurs in the majority of HCV-infected persons, and infection with the virus has become the main indication for liver transplantation. Initial diagnosis of HCV infection is classically done by serologic methods either by determining anti HCV antibody and by determining the presence of HCV RNA . HCV encodes a virus-specific helicase, protease, and polymerase, and because of the critical function of these proteins in the viral life cycle, they represent attractive targets for antiviral therapy.
Multiple myeloma (MM) is a plasmacell neoplasm. The diagnosis is performed on bone marrow aspirate or bone marrow biopsy that show the presence of plasmacells, associated to anemia, hypercalcemia, osteolytic bone lesions, real failure ( C.R.A.B features). It is important distinguish between monoclonal gammopathy of undetermined significance, asymptomatic (smoldering) multiple myeloma, symptomatic multiple myeloma, solitary plasmacytoma, and other plasma cell diseases based on the IMWG criteria . Diagnosis should be based on the following tests: detection and evaluation of the monoclonal (M-) component by serum and 24-h urine protein electrophoresis; quantification of IgG, IgA and IgM immunoglobulins; characterization of the heavy and light chains by immunofixation; serum-free light-chain measurement, evaluation of bone marrow plasma cell infiltration; evaluation of lytic bone lesions, through full skeleton X-ray survey or magnetic resonance imaging (MRI); biological assessments (b2-microglobulin, C-reactive protein, lactate dehydrogenase and serum albumin); cytogenetic and fish analysis, haemoglobin (and full blood cell counts), serum creatinine and calcium level.
Bortezomib is the drug used as first line therapy. It is a proteasome inhibitor. During treatment with bortezomib, rare cases of hepatic failure have been reported . lenalidomide is used an second line therapy , it belongs to the immunomodulatory drugs (IMiDs). No dedicated study has been conducted in patients with hepatic impairment, as the elimination of unchanged lenalidomide is predominantly by the renal route.
In this article we report a case of a 74-year-old women with MM and HCV-related disease treated with bortezomib and lenalidomide. In 2008 diagnosis of MGUS. From 1976 Hepatitis HCV-related disease after transfusion. During this period periodic abdominal ultrasound showed steatosis of liver and an increase of transaminases. No need of liver biopsy. In July 2011 it showed evolution in Multiple Myeloma. Stage IIA according to Durie and Salmon Stage, I Stage according to ISS Stage System. Principal characteristics at diagnosis: PLT 73.000/mmc, Hb 9.6 g/dl, WBC 4.100/mmc, Plasmacells 33%, SGOT 120 U/L , SGPT 93 U/L, Creatinine 1 mg/dl, IgG 3060 mg/dl, Calcium 8.4 mg/dl, Gammaglobulin 34.7%, Monoclonal Component 3.1 g/dL, Serum
Immunofixation IgG-Lambda, Urine Immunofixation Negative, Scheletal Survey Negative, MRI Negative, FISH Negative, Cytogenetics Negative, HCV-RNA 5.120.000 UI/ml. No antiviral therapy with acyclovir. So the patient was treated with bortezomib (1,3mg/m^2) and dexamethasone (20mg) day 1,8,15,22.
After 9 cycles of therapy, completed in August 2012, the patient obtained a VGPR (Very Good Partial Response), with an improvement of liver parameters and of the blood counts. SGOT 36 U/L, SGPT 35 U/L, HCV-RNA 2.120.000 UI/mL, PLT 90.0000/mmc. In August 2013 progression of the disease ( HCV-RNA 4.000.000 UI/mL) so the patient started therapy with lenalidomide (25 mg) and steroids dexamethasone 20 mg), still ongoing.
Currently normal liver parameters and blood counts. The last HCV RNA value is 1.390.000 UL/ml.
The efficacy of bortezomib and lenalidomide in multiple myeloma is known to everyone. In this report, we want to show that, although the patient has been affected by HCV-related liver disease for many years, treatment with bortezomib and lenalidomide allows to obtained a good response to myeloma. Moreover, despite the effectiveness of acyclovir is recognized in the literature in terms of reducing the hepatitis C virus , the HCV RNA value is decreased during treatment with bortezomib and lenalidomide without the use of it. Furthermore, the combination with steroids did not worsen the hepatic pathology.

Disclosures
No relevant conflicts of interest to declare.