Improved survival for dose-intensive chemotherapy in primary mediastinal B-cell lymphoma: a systematic review and meta-analysis of 4,068 patients

Abstract

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P<0.01). Survival benefit was maintained when analyzing rituximab only regimens; OS was 91% (95% CI: 89-93) for the rituximab-DI-CIT arm compared to 86% (95% CI: 82-89) for the R-CHOP-21 arm (P=0.03). Importantly, 55% (95% CI: 43-65) of the S-CIT group received RT compared to 22% (95% CI: 15-31) of DI-CIT patients (meta-regression P<0.01). To our knowledge, this is the largest meta-analysis reporting efficacy outcomes for the front-line treatment of PMBCL. DI-CIT demonstrates a survival benefit, with significantly less radiation exposure, curtailing long-term toxicities associated with radiotherapy. As we await results of randomized prospective trials, our study supports the use of dose-intensive chemoimmunotherapy for the treatment of PMBCL.

Figure 1.

PRISMA diagram depicting the identification, screening and inclusion/exclusion of studies.

Figure 2.

Forest plot comparing pooled overall survival for dose-intensive chemoimmunotherapy (DI-CIT) (left) and standard approach chemoimmunotherapy (S-CIT) (right) studies. Patient survival is recorded as the event next to total number of patients for each study.

Figure 3.

Forest plot comparing pooled consolidative mediastinal radiation for dose-intensive chemoimmunotherapy (DI-CIT) (left) and standard approach c he moimmunotherapy (S-CIT) (right) studies. Use of radiation is recorded as the event next to the total number of patients for each study.

Figure 4.

Graphical representation of the pooled primary and secondary outcomes for patients treated with dose-intensive chemoimmunotherapy (DI-CIT) compared to standard approach chemoimmunotherapy (S-CIT).