The role of central nervous system (CNS) prophylaxis in preventing DLBCL patients from CNS relapse: A network meta-analysis

Secondary central nervous system (CNS) relapses are an uncommon yet devastating complication in diffuse large B cell lymphoma (DLBCL). Although several prophylaxis attempts were employed clinically in order to reduce the CNS relapse rate, the optimal management remained uncertain.We employed conventional meta-analysis along with Network meta-analysis to investigate an optimal prophylactic strategy. The primary outcome was CNS relapse rate.A total of thirty-six studies comprising 5 RCTs, one clinical trial and 30 observational studies were included. Rituximab overall was superior in reducing CNS relapse rate, and the statistical significance exists (RR 0.79(0.68-0.93), p = 0.004). In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Intensive chemotherapy regimen containing HD-MTX with HD-Ara-C (SUCRA 93.4 %) was ranked as the first in reducing CNS relapse rate followed by no prophylaxis (SUCRA 57.5 %), HD-MTX (SUCRA 53.1 %), IT (SUCRA 34.5 %) and lenalidomide maintenance (SUCRA 11.5 %). In addition, intercalated HD-MTX had a trend of reducing CNS relapse but without statistical significance (RR 0.86(0.44-1.68), p = 0.67). However, i-HD-MTX was associated with increased grade 3-4 toxicities and prolonged inpatient stay. Early HD-MTX exposure also increased the treatment related death.Our network meta-analysis provides an overview of the relative efficacy of all available CNS prophylaxis strategies in DLBCL. In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Further studies with prospective, randomized clinical trials as well as with more focus on novel target agents that could spread blood-brain barriers are suggested.