Optimizing outcomes in primary mediastinal B-Cell lymphoma: is R-CHOP enough?

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is recognized as a unique clinicopathologic entity. It has a predilection for female adolescents and young adults, and is characterized by distinct morphologic, immunophenotypic, and molecular features. PMBL is rare, and this has resulted in a paucity of prospective data and lack of randomized studies, leading to controversy regarding optimal frontline therapy. In this issue of Blood Advances, Camus and colleagues describe real-world patient outcomes following frontline immunochemotherapy across 25 centers in France and Belgium.Three hundred and thirteen treatment-naïve patients with PMBL were retrospectively evaluated in the study. A total of 180 received rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP), 76 received rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone every 14 days (R-CHOP-14), and 57 received R-CHOP every 21 days (R-CHOP-21), respectively. Outcomes were excellent with high end-of-treatment (EOT) complete metabolic response rates between 76% and 86%, and mediastinal radiation was administered in just 5.4%. Progression-free survival at 3 years favored R-ACVBP and R-CHOP-14 (89.4%, 89.4%), with statistically lower rates for R-CHOP-21 (74.7%). Overall survival at 3 years also supported the dose-intensive options (R-ACVBP, 92.4%; R-CHOP-14, 100%; R-CHOP-21, 87.5%). The results presented here are of interest and importance, especially considering the high number of patients included, and the authors raise many provocative questions regarding optimal management of the disease. Despite this, the study is limited to answer the key question of whether or not increased dose-intensity approaches are superior to R-CHOP-21. Following R-ACVBP and R-CHOP-14 therapy, a low proportion of patients needed radiation. However, a significant number of these patients underwent consolidation transplantation (25.6% and 31.6%, respectively), which may have affected outcomes. Additionally, transplantation is associated with high added toxicity and is not a standard approach in upfront management of PMBL. Further data that confounds interpretation of results were the higher proportion of older patients (.60 years), who are frequently not considered candidates for doseintensive approaches, in the R-CHOP-21 cohort.Early retrospective studies in PMBL demonstrated that more aggressive chemotherapy regimens were associated with higher response rates in comparison with CHOP. 1 This has not proven to be the case in diffuse large B-cell lymphoma, where R-CHOP remains the optimal approach following comparisons with higher intensity, more toxic therapies. Higher sensitivity of PMBL to dose intensity may potentially be explained by its much younger age distribution as well as its close biological resemblance to classic Hodgkin lymphoma, a disease that benefits from increased therapeutic intensity. 2 Although R-CHOP has been commonly used in studies of PMBL, its use has relied quite significantly on consolidation m...

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

“…4 These hypothetical concepts have led to the investigation of dose-intensive chemoimmunotherapy (DI-CIT) for PMBCL, but currently there is a paucity of prospective randomized trials showing superiority of these treatment regimens compared to R-CHOP-21. 5 Thus, our study goal was to analyze all published first-line treatment data for PMBCL with either DI-CIT or standard approach chemoimmunotherapy (S-CIT), to evaluate differences in survival outcomes and reliance on mediastinal radiation.…”