Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy
Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy
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DOI：
10.1182/blood-2018-04-848044
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发表时间：
2019-01-10
期刊：
影响因子：
20.3
通讯作者：
Tobinai, Kensei
中科院分区：
文献类型：
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作者：
Kusumoto, Shigeru;Arcaini, Luca;Tobinai, Kensei
在3期戈亚和GALLIUM研究中，在接受含obinutuzumab或利妥昔单抗免疫化疗的HBV感染消退（乙型肝炎表面抗原阴性，乙型肝炎核心抗体阳性）的B细胞非霍奇金淋巴瘤（NHL）患者中评估了乙型肝炎病毒（HBV）再活化的风险。研究药物末次给药后每月至1年进行HBV DNA监测。如果HBV再激活（确认，HBV DNA >= 29 IU/mL），则停止免疫化疗并开始核苷（酸）类似物治疗（抢先NAT）。如果HBV DNA检测不到或未证实再激活，则重新开始免疫化疗，如果NAT检测到HBV DNA超过100 IU/mL，则停止免疫化疗。研究者可自行决定是否允许预防性NAT。在326例HBV感染消退的患者中，27例（8.2%）发生HBV再激活，发生时间中位数为首次给药后125天（四分位距，85-331天）。在232例未接受预防性NAT的患者中，25例（10.8%）发生HBV再激活;所有患者均接受了预防性NAT。94例患者接受了预防性NAT; 2例（2.1%）发生HBV再激活。无患者发生HBV相关肝炎。多变量考克斯分析显示，基线时可检测到的HBV DNA与再激活风险增加密切相关（调整后的风险比[HR]，18.22; 95%可信区间[CI]，6.04-54.93; P < .0001）。预防性NAT与风险降低密切相关（校正HR，0.09; 95%CI，0.02-0.41; P = .0018）。HBV DNA监测指导的预先NAT可有效预防HBV感染消退的B细胞NHL患者在抗CD 20免疫化疗期间发生HBV相关肝炎。抗病毒预防也是有效的，可能适用于高危患者。这些试验在www.clinicaltrials.gov上注册为NCT 01287741（戈亚）和NCT 01332968（GALLIUM）。
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).