The role of maintenance therapy in patients with diffuse large B cell lymphoma: A systematic review and meta-analysis

Randomized trials of maintenance therapy (MT) in diffuse large B cell lymphoma (DLBCL) are inconclusive regarding its effect on overall survival (OS) and disease control. We aimed to examine the efficacy and safety of MT in this meta-analysis. Systematic review and meta-analysis of randomized controlled trials comparing MT with observation or placebo, in patients with DLBCL, who achieved complete response (CR) or partial response (PR) after first-line chemotherapy with or without rituximab. Primary outcome was OS. Secondary outcomes included relapse rate, disease control (defined as progression-free survival, event-free survival, or disease-free survival, as reported in the original trials), and safety. Our search yielded 14 trials including 5122 patients. Median age of patients was 49 to 70 years. Six trials included rituximab as the MT; three included Interferon alfa; other trials include thalidomide, lenalidomide, cyclophosphamide and prednisone, serine threonine kinase inhibitor enzastaurin, and mTOR inhibitor everolimus. MT did not improve OS compared to observation, OR 0.91, (95% CI 0.78-1.07). Results were the same in a subgroup analysis by the type of maintenance (rituximab vs other). MT did decreased relapse rate, RR 0.76 (95% CI 0.65-0.89) and improved disease control, OR 0.74 (95% CI 0.65-0.84). Disease control was significantly improved in the subgroup of studies evaluating rituximab as maintenance OR 0.61 (95% CI 0.47-0.79) and in the subgroup of R-CHOP induction studies OR 0.77 (95% CI 0.67-0.88). Serious or grade III/IV adverse events including neutropenia and infections were significantly more common in the maintenance arm, RR = 1.69 (95% CI 1.29-2.22). MT in patients with DLBCL achieving CR or PR after induction therapy did not affect OS, yet it decreased relapse rate and improved disease control at the cost of higher infection rate. Our data do not support routine administration of MT in patients with DLBCL.