Efficacy of rituximab maintenance therapy for aggressive B-cell lymphoma depends on use of rituximab in induction therapy: a meta-analysis of randomized controlled trials

Abstract

Contrary to the established role of rituximab maintenance therapy for advanced follicular lymphoma with a high tumor burden, 1 it remains controversial as to whether rituximab confers advantageous effects for aggressive lymphoma when used as maintenance therapy. Recently, a cardinal study from an Austrian group reported the results of the randomized NHL13 trial, which demonstrated no significant prolongation in event-free survival (EFS) by adding rituximab maintenance for patients with aggressive lymphoma who achieved CR/CRu with R-CHOP-like regimens.2 The interpretation of this study and previous trials featuring rituximab maintenance for aggressive lymphoma, suffers from the problem of inconsistent results, which are probably attributable to the different study designs among trials. Therefore, we conducted a meta-analysis to inquire into those features connected to the benefits associated with rituximab maintenance.We extracted studies by searching Medline (years dating from 1960 to May 2015), The Cochrane Library, and ongoing and unpublished trials.3,4 The terms "rituximab", "maintenance", and "lymphoma" were cross-searched. Out of the 739 candidate papers and clinical study registries, we extracted prospective randomized controlled trials where case cohorts were administered with single-agent rituximab as maintenance therapy for responding patients (PR or better) to induction treatments, with or without consolidative autologous stem-cell transplantation (ASCT), and were compared with control cohorts who were followed with observation alone. Studies focusing mainly on mantle cell lymphoma were excluded as the basic treatment scheme for mantle cell lymphoma differs to that for aggressive lymphoma. As a result, we extracted 4 relevant reports.2-5-7 The details of these studies are shown in Table 1. Three studies targeted untreated patients and the other targeted patients with relapsed/refractory status. Induction regimens included rituximab in two studies, and not in one. The remaining study had randomized patients into two arms of those receiving rituximab-containing and non-rituximab containing regimens before maintenance therapy, thus patients in this study were divided into rituximabnaïve or not in the subgroup analysis.6 The pooled estimates of the effect were calculated using the random effects model using the DerSimonian-Laird method with inverse-variance weighting. Hazard ratio (HR) was selected to measure responses, and adverse effects were evaluated by using risk difference (RD). Three of the studies examined event-free survival (EFS) and one examined failure-free survival (FFS), and we used these parameters to estimate treatment effects, considering the similarity of endpoints. When HR was not available for a given study, data measurement was estimated using methods described by Tierney et al. 8 We assessed the heterogeneity of the trial results using a chi-squared test of heterogeneity and the I 2 measure of inconsistency. We analyzed the data for the 1546 patients with aggressive lymphoma from the...

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

“…The efficacy of rituximab as maintenance therapy in DLBCL was previously evaluated in 3 meta-analysis of RCTs. [24][25][26] One meta-analysis by Nannya et al 24 The third meta-analysis, published by Zhou et al, 26 included 5 RCTs 2, [16][17][18]27 and concluded that males and previously untreated DLBCL patients benefited most from maintenance treatment in terms of EFS and PFS when rituximab was the maintenance therapy.…”

Low‐dose rituximab every 6 months for the treatment of acetylcholine receptor–positive refractory generalized myasthenia gravis

“…Most studies have implemented high-dose strategies that are used in lymphoma treatment. 11 Nevertheless, several studies have indicated that low-dose rituximab is sufficiently potent to be effective in treating refractory MG, 6,12 and a minimum of two cycles are needed to prevent potential relapses. 13 A systematic review recommended that a repeat rituximab infusion should be considered 4 to 6 months after a cycle.…”

“…The rituximab dose regimens have not been consistent. Most studies have implemented high‐dose strategies that are used in lymphoma treatment . Nevertheless, several studies have indicated that low‐dose rituximab is sufficiently potent to be effective in treating refractory MG, and a minimum of two cycles are needed to prevent potential relapses .…”

Frontline treatment of diffuse large B‐cell lymphoma: Beyond R‐CHOP

“…84 Maintenance therapy showed no benefit in EFS when rituximab was used as part of induction therapy and in patients who had prior ASCT. 84 Another meta-analysis included seven studies of 1470 patients with DLBCL who received maintenance rituximab following chemoimmunotherapy induction and in the salvage setting. 85 Rituximab maintenance statistically improved EFS but not OS.…”