Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity

Fernández Rodríguez, M. Concepción; Rodríguez-Sevilla, Juan José; Fernández-Ibarrondo, Lierni; Sánchez González, Blanca; Gibert Fernandez, Joan, 1988-; Bento, Leyre; García, Juan Fernando; Sancho, Juan Manuel; Díez-Feijóo, Ramón; Camacho Díaz, Laura; García Retortillo, Montserrat; Gimeno Vázquez, Eva; Colomo Saperas, Luis Alberto; Gutiérrez, Antonio; Bellosillo Paricio, Beatriz; Salar, Antonio

doi:http://dx.doi.org/10.1182/bloodadvances.2021005316

Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity

Citation

Fernández-Rodríguez C, Rodríguez-Sevilla JJ, Fernández-Ibarrondo L, Sánchez-González B, Gibert J, Bento L, et al. Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity. Blood Adv. 2022 Jan 11; 6(1): 82-6. DOI: 10.1182/bloodadvances.2021005316

Abstract

Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc- cases (68.1 vs 57.2 years; P = .007) and higher β2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.