Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy
A partir de données de deux essais de phase III incluant 326 patients atteints d'un lymphome à cellules B et ne présentant plus d'indicateurs d'une infection par le virus de l'hépatite B, cette étude évalue l'effet d'un traitement à base d'obinutuzumab ou de rituximab sur le risque de réactivation de l'infection virale
Résumé en anglais
Risk of 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 obinutuzumab or rituximab. In case of HBV reactivation (confirmed, quantifiable HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (NAT) started (preemptive NAT). Immunochemotherapy was restarted if HBV DNA became undetectable or if reactivation was not confirmed. Immunochemotherapy was 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 (21 with HBV DNA ≥100 IU/mL), occurring a median of 125 days (IQR, 85-331) after first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Among 94 patients with prophylactic NAT, 2 (2.1%) had HBV reactivation: 1 after stopping NAT and 1 while on NAT (lamivudine). 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, 18.22; 95% CI, 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted hazard ratio, 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. The studies are registered to https://clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).
