Hepatitis B Reactivation in a Multiple Myeloma Patient with Resolved Hepatitis B Infection during Bortezomib Therapy : Case Report

Tanaka, Hiroaki; Sakuma, Ikuo; Hashimoto, Shinichiro; Takeda, Yusuke; Sakai, Shio; Takagi, Toshiyuki; Shimura, Takanori; Nakaseko, Chiaki

doi:10.3960/jslrt.52.67

Cited by 26 publications

(22 citation statements)

References 12 publications

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“…The risk of HBV reactivation is well described in patients with lymphoma, especially after the use of rituximab (reference). However, for MM there are just a few case reports that described the risk of HBV reactivation after cytotoxic chemotherapy 38,39 , 19,40 . In these case reports most patients were receiving steroids, proteasome inhibitors or immunomodulatory agents, and very few had undergone an auto-HCT 38,39,40 .…”

Section: Discussionmentioning

confidence: 99%

Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Varma

Biritxinaga

Saliba

et al. 2017

Biology of Blood and Marrow Transplantation

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Background Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. We evaluated the incidence of hepatitis B reactivation and liver toxicity in patients with multiple myeloma (MM) who received high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. Methods We identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control) who were matched for age, time of auto-HCT, disease status and preparative regimen. Both groups received HDC and auto-HCT between 1991 and 2013. Primary endpoints were: 1) HBV reactivation defined as HBsAg positivity or ≥10-fold increase in HBV DNA; 2) hepatotoxicity, as defined in NCI CTCv3.0. Results Approximately 70% in each group received melphalan alone as preparative regimen. In the resolved HBV infection group, 52 patients (49%) were Hepatitis B surface antibody (HBsAb) positive, and 24 (22%) had detectable HBV DNA prior to auto-HCT. Serum HBV DNA level was <100 IU/m in 22 patients, and <300 IU/ml in 2 patients. Hepatitis B e antigen (HBeAg) was non-reactive in all 4 patients evaluated prior to auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with Lamivudine, while 4 patients received Lamivudine (3) or Tenofovir (1) at reactivation for a median duration of 1 year. HBV reactivation was seen in 7 of 107 (6.5%) patients in the resolved HBV group. There was a ≥10-fold increase in HBV DNA in 5 of 7 patients with HBV reactivation, and 2 of 7 also became positive for HBeAg. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or more hepatotoxicity in resolved HBV infection and the control groups was 30% and 22%, respectively (hazard ratio [HR] 1.3; 95% confidence interval [CI], 0.7–2.3; P = 0.4). There was a trend for higher NRM in the control group at 1 year 7% vs 1%, with a HR of 0.15 (95% CI 0.02–1.2, P = 0.08) and at 2 years 8% vs 1% with a HR of 0.13 (95% CI 0.02–1.1, P= 0.06) after auto-HCT. With a median follow up of 18 and 35 months in resolved HBV infection vs. control groups, the median progression free survival was 21 and 18 months (p=0.5), respectively. Median overall survival in resolved HBV infection and control groups was 53 vs. 67 months (p=0.2), respectively. Conclusion Resolved HBV infection is associated with a significant risk of HBV reactivation and hepatotoxicity in patients undergoing auto-HCT for MM. These complications were reversible and were not associated with a decrease in PFS or OS.

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Section: Discussionmentioning

confidence: 99%

Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Varma

Biritxinaga

Saliba

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Tanaka et al [7] reported the case of a 72-year-old male with remote HBV infection who underwent reactivation after receiving 10 courses of BOR and dexamethasone (DEX). Both were immediately discontinued and he was started on entecavir.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib Induced Hepatitis B Reactivation

Hussain

Jhaj

Ahsan

et al. 2014

Case Reports in Medicine

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Background. It has recently been reported that hepatitis B (HBV) reactivation often occurs after the use of rituximab and stem cell transplantation in patients with lymphoma who are hepatitis B surface antigen (HBsAg) negative. However, clinical data on HBV reactivation in multiple myeloma (MM) is limited to only a few reported cases. Bortezomib and lenalidomide have remarkable activity in MM with manageable toxicity profiles, but reactivation of viral infections may emerge as a problem. We present a case of MM that developed HBV reactivation after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with a history of marginal cell lymphoma was monitored without requiring therapy. In 2009, she developed MM, presenting as a plasmacytoma requiring vertebral decompression and focal radiation. While receiving radiation she developed renal failure and was started on bortezomib and liposomal doxorubicin. After a transient response to 5 cycles, treatment was switched to lenalidomide. Preceding therapy initiation, her serology indicated resolved infection. Serial monitoring for HBV displayed seroconversion one month after change in therapy. Conclusion. Bortezomib associated late HBV reactivation appears to be a unique event that requires further confirmation and brings to discussion whether hepatitis B core positive individuals would benefit from monitoring of HBV activation while on therapy.

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“…Interestingly, our patient in Case 1 developed HBsAg seroreversion with only transient hepatitis before entering what looked like the immune tolerant phase. There have only been 2 previous reported cases of patients with MM who received Bortezomib and had HBV reactivation followed directly by an immunotolerant phase [10, 11]. …”

Section: Discussionmentioning

confidence: 99%

“…ASCT has also been raised as a risk factor for HBV reactivation [15]. Bortezomib, a proteasome inhibitor, has been previously reported in a few cases of HBV reactivation in MM patients [10, 11]. Given its mechanism of action, Bortezomib may impair intracellular viral antigen processing leading to impaired maintenance of T-cell memory [16].…”

Section: Discussionmentioning

confidence: 99%

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Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant

Almaghrabi

Fortinsky

Wong

2017

Case Reports in Hepatology

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Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.

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Hepatitis B Reactivation in a Multiple Myeloma Patient with Resolved Hepatitis B Infection during Bortezomib Therapy : Case Report

Cited by 26 publications

References 12 publications

Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Bortezomib Induced Hepatitis B Reactivation

Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant

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