HBV reactivation in a HBsAg-negative patient with multiple myeloma treated with prednisolone maintenance therapy after autologous HSCT

Gu, Ha Ra; Shin, Dong Yeop; Choi, Hong Seok; Moon, Chae Ho; Park, Su Cheol; Kang, Hye Jin

doi:10.5045/br.2015.50.1.51

Cited by 9 publications

(5 citation statements)

References 11 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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“…[ 6 7 8 9 10 ] However, bortezomib-based regimens usually contain glucocorticoid, which has a negative effect on HBV infection, [14] and maintenance therapy with prednisolone can also result in HBV reactivation in patients of multiple myeloma. [15] Moreover, studies have shown that autologous HSc transplantation is one of the important risk factors for HBV reactivation. [ 16 17 ] These factors also influence the assessment of the role of bortezomib in HBV reactivation.…”

Section: Discussionmentioning

confidence: 99%

Clearance of HBsAg in a patient with familial multiple myeloma after a bortezomib-based regimen combined with anti-HBV drug

Zhang

Liang²,

Li³

et al. 2020

Medicine

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Rationale: Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. Patient concerns: A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. Diagnoses: The diagnosis was MM with chronic carrier of HBV. Interventions: He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. Outcomes: This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. Lessons: This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.

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“…Retrospective reports summarizing HBV reactivation in MM patients, including case reports, included a total of 125 cases [8,22,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68] (Table 4 and Table 5). All 16 cases with HBV reactivation through 2010 underwent HSCT [56,57,58,59,60,61].…”

Section: Hbv Reactivation In MM Patientsmentioning

confidence: 99%

Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma

Tsukune

Sasaki

Komatsu

2019

Cancers

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Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of fulminant hepatitis. The preventive strategy for HBV reactivation in patients with malignant lymphoma has already been established based on some prospective studies. As there was an increased number of novel agents being approved for the treatment of multiple myeloma (MM), the number of reported cases of HBV reactivation among MM patients has gradually increased. We conducted a Japanese nationwide retrospective study and revealed that HBV reactivation in MM patients is not rare and that autologous stem cell transplantation is a significant risk factor. In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required.

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HBV reactivation in a HBsAg-negative patient with multiple myeloma treated with prednisolone maintenance therapy after autologous HSCT

Cited by 9 publications

References 11 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

Clearance of HBsAg in a patient with familial multiple myeloma after a bortezomib-based regimen combined with anti-HBV drug

Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma

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