Distinct immunologic kinetics and cytomegalovirus reactivation incidence with rituximab- versus obinutuzumab–bendamustine in follicular lymphoma: a single-center case series study

Rituximab and obinutuzumab, anti-CD20 monoclonal antibodies, are widely employed for treatment of follicular lymphoma (FL) by targeting both neoplastic and normal CD20-expressing B lymphocytes, consequently inducing immunosuppression. In this condition, viral reactivations are common and represent a major cause of morbidity and mortality. In this single-center two-arm observational real-life study, we evaluated incidence, immunological and serological status, and clinical outcomes of cytomegalovirus (CMV) reactivation in FL patients treated with bendamustine + rituximab (R-BENDA; N = 23) or obinutuzumab (G-BENDA; N = 23). CMV reactivation more frequently occurred in patients treated with R-BENDA compared to G-BENDA (P = 0.022), and immune kinetics showed significant differences between the two groups, with a deeper and earlier immunosuppression in R-BENDA treated subjects. Moreover, R-BENDA group displayed a significant higher risk of CMV reactivation compared to G-BENDA (hazard ratio, 2.232; 95% confidence interval 1.107–4.500; P = 0.0249). However, G-BENDA patients tended to have a shorter 5-year overall survival (59% vs. 86.7%, G-BENDA vs. R-BENDA; P = 0.0903). By multivariate analysis, B symptoms were an independent predictor of CMV reactivation, and high baseline SUV as an additional risk factor in R-BENDA patients. In conclusion, anti-CD20 agent could increase the risk of CMV reactivation in FL patients, especially in R-BENDA treated subjects who experienced early and deep immunosuppression. Therefore, close monitoring of clinical and laboratory data may improve outcomes in FL patients by preventing CMV disease, especially in those treated with rituximab who are more prone to viral reactivation. However, larger prospective studies are required to confirm our preliminary results.