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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 and Kensei Tobinai

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Analysis population and patient flow. benda, bendamustine; CVP, cyclophosphamide, vincristine, prednisone; G, obinutuzumab; MZL, marginal zone lymphoma; R, rituximab. *The 2 patients with HBV reactivation who had received prophylactic NAT had their study treatment withheld until their HBV DNA returned to undetectable levels; neither patient developed HBV-related hepatitis. †None of 25 patients with HBV reactivation who were treated with preemptive NAT developed HBV-related hepatitis.

  • Figure 2.

    Time to HBV reactivation in anti–HBc-positive patients by receipt of prophylactic NAT (analysis population, n = 326).

Tables

  • Table 1.

    Patient demographics and disease characteristics at baseline by treatment arm in patients with positive anti-HBc serology (analysis population, n = 326)

    CharacteristicG-Chemo (n = 155)R-Chemo (n = 171)
    Median age, y (range)61 (25-81)59 (19-83)
    Female, n (%)60 (38.7)81 (47.4)
    Race, n (%)
     White49 (31.6)64 (37.4)
     Black3 (1.9)0
     Asian103 (66.5)105 (61.4)
     Other02 (1.2)
    Region, n (%)
     East Asia*86 (55.5)89 (52.0)
     Europe48 (31.0)57 (33.3)
     Other21 (13.5)25 (14.6)
    Lymphoma type, n (%)
     DLBCL (GOYA)121 (78.1)114 (66.7)
     FL (GALLIUM)29 (18.7)53 (31.0)
     MZL (GALLIUM)5 (3.2)4 (2.3)
    HBV serology, n (%)
     Anti-HBc+, anti-HBs+94 (60.6)113 (66.1)
     Anti-HBc+, anti-HBs-57 (36.8)52 (30.4)
     Missing anti-HBs4 (2.6)6 (3.5)
    HBV DNA <29 IU/mL at baseline, n (%)
     Not detectable143 (92.3)157 (91.8)
     Detectable, but not quantifiable7 (4.5)4 (2.3)
     Missing5 (3.2)10 (5.8)
    ECOG performance status, n (%)
     076 (49.0)81 (47.4)
     168 (43.9)69 (40.4)
     211 (7.1)21 (12.3)
    IPI risk category (GOYA), n (%)n = 121n = 114
     High20 (16.5)18 (15.8)
     High-intermediate41 (33.9)31 (27.2)
     Low-intermediate38 (31.4)42 (36.8)
     Low22 (18.2)23 (20.2)
    FLIPI-1 risk category (GALLIUM, FL), n (%)n = 29n = 53
     High11 (37.9)21 (39.6)
     Intermediate10 (34.5)19 (35.8)
     Low8 (27.6)13 (24.5)
    IPI risk category (GALLIUM, non-FL), n (%)n = 5n = 4
     High1 (20.0)0
     High-intermediate2 (40.0)2 (50.0)
     Low-intermediate1 (20.0)1 (25.0)
     Low1 (20.0)1 (25.0)
    Prophylactic NAT, n (%)40 (25.8)54 (31.6)
     Lamivudine33 (21.3)46 (26.9)
     Entecavir7 (4.5)8 (4.7)
    Treatment, n (%)
     CHOP141 (91.0)§148 (86.5)
     Benda13 (8.4)19 (11.1)
     CVP1 (0.6)4 (2.3)
    • Benda, bendamustine; Chemo, chemotherapy; CVP, cyclophosphamide, vincristine, and prednisone; ECOG, Eastern Cooperative Oncology Group; FLIPI, Follicular Lymphoma International Prognostic Index; G, obinutuzumab; IPI, International Prognostic Index; MZL, marginal zone lymphoma; R, rituximab.

    • * East Asia includes China, Japan, South Korea, and Taiwan.

    • Europe includes Belgium, Czech Republic, Germany, Hungary, Italy, Russia, Spain, Switzerland, and the United Kingdom.

    • Other includes Australia, Canada, and Thailand.

    • § G-CHOP: GOYA, n = 121; GALLIUM, n = 20.

    • R-CHOP: GOYA, n = 114; GALLIUM, n = 34.

  • Table 2.

    Cox regression analysis for time to HBV reactivation (analysis population, n = 326)

    Effect/covariate*Time to HBV reactivation (univariate)Time to HBV reactivation (multivariate)
    Crude HR95% CIPAdjusted HR95% CIP
    Age at baseline (continuous, by 10 y)1.240.90-1.79.22601.631.00-2.37.0351
    Sex (male vs female)1.510.68-3.37.31101.190.50-2.86.6923
    ECOG performance status at baseline (2 vs 0 or 1)1.040.25-4.42.9531NANANA
    Lymphoma type (DLBCL [GOYA] vs non-DLBCL [GALLIUM])3.061.04-9.04.04303.761.09-12.96.0356
    IPI, FLIPI score (high-intermediate/high vs low/intermediate/low-intermediate)1.510.71-3.21.2877NANANA
    Anti-HBs at baseline (negative vs positive)4.351.93-9.78.00044.001.71-9.37.0014
    HBV DNA level at baseline, IU/mL (detectable vs not detectable)12.424.96-31.07<.000118.226.04-54.93<.0001
    Prophylactic NAT (yes vs no)0.190.04-0.79.02260.090.02-0.41.0018
    Antibody treatment group (G-Chemo vs R-Chemo)1.940.89-4.24.09631.790.78-4.16.1748
    Chemotherapy group§ (CHOP vs non-CHOP)1.860.44-7.94.3990NANANA
    • NA, not applicable.

    • * Reference groups for each factor are shown in bold. Race/ethnicity was not included in the model.

    • Factors with P < .2 by univariate analysis, baseline age, and sex were included in the multivariate analysis; 95% Wald confidence interval and P value for Wald test.

    • Includes DLBCL patients from GOYA and non-DLBCL patients from GALLIUM.

    • § Includes patients from both GOYA and GALLIUM.