Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

Shigeru Kusumoto; Luca Arcaini; Xiaonan Hong; Jie Jin; Won Seog Kim; Yok Lam Kwong; Marion G. Peters; Yasuhito Tanaka; Andrew D. Zelenetz; Hiroshi Kuriki; Günter Fingerle-Rowson; Tina Nielsen; Eisuke Ueda; Hanna Piper-Lepoutre; Gila Sellam; Kensei Tobinai

doi:10.1182/blood-2018-04-848044

Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

Shigeru Kusumoto^*, Luca Arcaini, Xiaonan Hong, Jie Jin, Won Seog Kim, Yok Lam Kwong, Marion G. Peters, Yasuhito Tanaka, Andrew D. Zelenetz, Hiroshi Kuriki, Günter Fingerle-Rowson, Tina Nielsen, Eisuke Ueda, Hanna Piper-Lepoutre, Gila Sellam, Kensei Tobinai

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

Abstract

Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ‡29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P 5 .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www. clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

Original language	English (US)
Pages (from-to)	137-146
Number of pages	10
Journal	Blood
Volume	133
Issue number	2
DOIs	https://doi.org/10.1182/blood-2018-04-848044
State	Published - Jan 10 2019

Funding

The authors would like to acknowledge the important contributions made by the investigators and the clinical and safety teams for the GALLIUM and GOYA trials. The current studies were sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of S.K., was provided by Louise Profit, Cheryl Wright, and Scott Malkin of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd. The current studies were sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of S.K., was provided by Louise Profit, Cheryl Wright, and Scott Malkin of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd.

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood-2018-04-848044

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Kusumoto, S., Arcaini, L., Hong, X., Jin, J., Kim, W. S., Kwong, Y. L., Peters, M. G., Tanaka, Y., Zelenetz, A. D., Kuriki, H., Fingerle-Rowson, G., Nielsen, T., Ueda, E., Piper-Lepoutre, H., Sellam, G., & Tobinai, K. (2019). Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy. Blood, 133(2), 137-146. https://doi.org/10.1182/blood-2018-04-848044

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title = "Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy",

abstract = "Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ‡29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P 5 .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www. clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).",

author = "Shigeru Kusumoto and Luca Arcaini and Xiaonan Hong and Jie Jin and Kim, {Won Seog} and Kwong, {Yok Lam} and Peters, {Marion G.} and Yasuhito Tanaka and Zelenetz, {Andrew D.} and Hiroshi Kuriki and G{\"u}nter Fingerle-Rowson and Tina Nielsen and Eisuke Ueda and Hanna Piper-Lepoutre and Gila Sellam and Kensei Tobinai",

note = "Publisher Copyright: {\textcopyright} 2019 by The American Society of Hematology.",

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doi = "10.1182/blood-2018-04-848044",

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Kusumoto, S, Arcaini, L, Hong, X, Jin, J, Kim, WS, Kwong, YL, Peters, MG, Tanaka, Y, Zelenetz, AD, Kuriki, H, Fingerle-Rowson, G, Nielsen, T, Ueda, E, Piper-Lepoutre, H, Sellam, G & Tobinai, K 2019, 'Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy', Blood, vol. 133, no. 2, pp. 137-146. https://doi.org/10.1182/blood-2018-04-848044

TY - JOUR

T1 - Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

AU - Kusumoto, Shigeru

AU - Arcaini, Luca

AU - Hong, Xiaonan

AU - Jin, Jie

AU - Kim, Won Seog

AU - Kwong, Yok Lam

AU - Peters, Marion G.

AU - Tanaka, Yasuhito

AU - Zelenetz, Andrew D.

AU - Kuriki, Hiroshi

AU - Fingerle-Rowson, Günter

AU - Nielsen, Tina

AU - Ueda, Eisuke

AU - Piper-Lepoutre, Hanna

AU - Sellam, Gila

AU - Tobinai, Kensei

PY - 2019/1/10

Y1 - 2019/1/10

N2 - Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ‡29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P 5 .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www. clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

AB - Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ‡29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P 5 .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www. clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

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Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

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