Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy

Abstract

Background:Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.Methods:We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled.Results:Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94), P = 0.02], progression-free survival (PFS) [HR = 0.61, 95% CI (0.52-0.72), P < 0.05], odds ratio (OR) [RR = 1.26, 95% CI (1.07-1.47), P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65) P =0.001].Conclusions:After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it's not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.

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.…”

“…included 4 RCTs,2,17,18 of which one included patients after autologous stem cell transplantation 27. This meta-analysis demonstrated that males had a higher EFS and lower rate of adverse effects compared to females when rituximab maintenance was administered, and that rituximab improved EFS only when it was not used also in the induction phase.The second meta-analysis published by Ren et al25 included 3 RCTs using rituximab maintenance, 2,17,18 and 4 RCTs using rituximab therapy as part of the salvage chemotherapy in the relapse setting and not as maintenance. This meta-analysis demonstrated that maintenance therapy with rituximab had no statistically significant effect on OS or EFS.…”

Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era

“…The National Comprehensive Cancer Network-International Prognostic Index for diffuse large B-cell lymphoma (DLBCL) could be a good example for our deduction, which has stronger prognostic value compared with original IPI for patients treated in the rituximab era who have an ameliorated outcome. [910] Furthermore, all the 5000 patients in the original IPS study were from western countries. Whether IPS applies to Chinese people remains to be explored.…”

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

“…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. Taken together, these results do not justify the administration of rituximab maintenance after induction treatment with standard R-CHOP.…”