Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study

Background:The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China. Methods:From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study. Results:The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12). Conclusions:Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.

[1]  W. Hwang,et al.  Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  S. Jee,et al.  Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study. , 2010, The Lancet. Oncology.

[3]  M. Boccadoro,et al.  Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial , 2010, Haematologica.

[4]  S. Beysel,et al.  Bortezomib-associated late hepatitis B reactivation in a case of multiple myeloma. , 2010, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[5]  M. Raaben,et al.  The Proteasome Inhibitor Velcade Enhances rather than Reduces Disease in Mouse Hepatitis Coronavirus-Infected Mice , 2010, Journal of Virology.

[6]  F. Sugauchi,et al.  Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma: two case reports , 2010, International journal of hematology.

[7]  F. Chisari,et al.  Bortezomib Inhibits Hepatitis B Virus Replication in Transgenic Mice , 2009, Antimicrobial Agents and Chemotherapy.

[8]  Yu Wang,et al.  Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. , 2009, Vaccine.

[9]  B. Moss,et al.  Inhibition of the Ubiquitin-Proteasome System Prevents Vaccinia Virus DNA Replication and Expression of Intermediate and Late Genes , 2009, Journal of Virology.

[10]  Hung-Jen Liu,et al.  Proteasome inhibition reduces avian reovirus replication and apoptosis induction in cultured cells , 2008, Journal of Virological Methods.

[11]  D. Dingli,et al.  Improved survival in multiple myeloma and the impact of novel therapies. , 2008, Blood.

[12]  P. Sonneveld,et al.  Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  H. Einsele,et al.  Bortezomib in combination with intermediate‐dose dexamethasone and continuous low‐dose oral cyclophosphamide for relapsed multiple myeloma , 2007, British journal of haematology.

[14]  M. Boccadoro,et al.  Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. , 2007, Blood.

[15]  C. Amici,et al.  Antiviral Activity of Proteasome Inhibitors in Herpes Simplex Virus-1 Infection: Role of Nuclear Factor-κB , 2006, Antiviral therapy.

[16]  X. Si,et al.  Ubiquitination Is Required for Effective Replication of Coxsackievirus B3 , 2006, PloS one.

[17]  S. Jagannath,et al.  Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma , 2005, British journal of haematology.

[18]  D. Esseltine,et al.  PAD combination therapy (PS‐341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma , 2005, British journal of haematology.

[19]  S. Montoto,et al.  Bortezomib-induced severe hepatitis in multiple myeloma: a case report. , 2005, Archives of internal medicine.

[20]  U. Schubert,et al.  The ubiquitin–proteasome system in HIV replication: potential targets for antiretroviral therapy , 2005, Expert review of anti-infective therapy.

[21]  M. Lai,et al.  The Ubiquitin-Proteasome System Facilitates the Transfer of Murine Coronavirus from Endosome to Cytoplasm during Virus Entry , 2005, Journal of Virology.

[22]  B. McManus,et al.  Proteasome inhibition reduces coxsackievirus B3 replication in murine cardiomyocytes. , 2003, The American journal of pathology.

[23]  Bart Barlogie,et al.  A phase 2 study of bortezomib in relapsed, refractory myeloma. , 2003, The New England journal of medicine.

[24]  M. Raamsman,et al.  Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier , 2000, Journal of Virology.

[25]  B. Thiers.  Analysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study , 2009 .