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 = .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).

• Authors: 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
• Journal: Blood (Blood) Vol. 133 Issue 2 Pg. 137-146 (01 10 2019) ISSN: 1528-0020 [Electronic] United States
• PMID: 30341058 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• Antiviral Agents
• DNA, Viral
• Rituximab
• obinutuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antineoplastic Agents, Immunological (adverse effects)
• Antiviral Agents (therapeutic use)
• DNA, Viral (genetics)
• Female
• Follow-Up Studies
• Hepatitis B (chemically induced, drug therapy, virology)
• Hepatitis B virus (drug effects, genetics)
• Humans
• Immunotherapy (adverse effects)
• Lymphoma, B-Cell (drug therapy, immunology, virology)
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Rituximab (adverse effects)
• Virus Activation (drug effects)