This article was written by Dr Mary Gleeson from the Royal Marsden Hospital in London and Surrey and her co-authors from various centers around the UK, and was published in the British Journal of Haematology on 1st of August 2016. The article describes the data from a subgroup analysis that evaluated the outcomes of patients (n=50) with primary mediastinal B-cell lymphoma (PMBL), which is a distinct type of diffuse large B-cell lymphoma (DLBCL); treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) with or without radiotherapy (RT) within the randomized phase III UK NCRI R-CHOP-14 trial (six cycles of R-CHOP every 14 days plus 2 cycles of rituximab) versus the R-CHOP-21 trial (8 cycles of R-CHOP every 21 days). The primary endpoint of the study was to determine overall survival (OS) and the secondary endpoints were to evaluate progression free survival (PFS) and response rate. Response following chemotherapy with R-CHOP was evaluated by computer tomography (CT) scans of the thorax, abdomen and pelvis with or without neck.
The main findings of the study were as follows:
- Fifty of the 1,080 patients (4.63%) had primary mediastinal B-cell lymphoma (WHO 2008 clinical criteria) and received either R-CHOP-21 (n=28) or R-CHOP-14 (n=22, 44%).
- After a median follow-up of 7.2 years, the 5-year OS was 83.8% (95% CI 73.4-94.2) and although OS was superior in the R-CHOP-21, the difference between the two arms just approached significance (p=0.06). More events occurred in the R-CHOP-21 group (8 out of 9 deaths).
- The 5-year PFS was reported to be 79.8% (95% CI 68.6-91.0) and there was no significant difference between the two regimens (p=0.1).
- After completion of chemotherapy, response rates, evaluated by CT, were as follows: CR = 42.9%, PR = 49% and stable disease = 2%. RT was administered to 58% of patients (n=29).
- Nine out of ten deaths occurred during the study. Patients either died due to progressive disease (n=7), cardiac-related (n=1) or due to an unknown cause (n=1). Five out of ten had disease progressions and 4/9 deaths occurred in patients who had received RT consolidation post-R-CHOP.
Although it was the largest PMBL cohort treated by R-CHOP, the number of patients was small and therefore more robust studies need to be established that would have more significant multivariate analysis; however, the data demonstrated in this study does provide evidence of R-CHOP efficacy in the management of PMBL and provides the ground work for other clinical trials. Dose-intensity should also be considered in future trials for this specific subtype of DLBCL.
We performed a subgroup analysis of the phase III UK National Cancer Research Institute R-CHOP-14 versus R-CHOP-21 (two- versus three-weekly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) trial to evaluate the outcomes for 50 patients with World Health Organization 2008 classified primary mediastinal B-cell lymphoma identified from the trial database. At a median followup of 7.2 years the 5-year progression-free survival and overall survival was 79.8% and 83.8%, respectively. An exploratory analysis raised the possibility of a better outcome in those who received R-CHOP-14 and time intensification may still, in the rituximab era, merit testing in a randomised trial in this subgroup of patients.
Gleeson M. et al. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol 2016 Aug 1. doi: 10.1111/bjh.14287. [Epub ahead of print].