Primary Mediastinal B-Cell Lymphoma (PMBCL) (BSH 2019)
Intro
Epidemiology
2-4% of all Non-Hodgkin lymphomas
Female > Male
Pathology
Distinct from DLBCL
Some overlap with classical Hodgkin lymphoma (>80% cases CD30+)
Cell of origin: Germinal centre or post-germinal centre thymic B lymphocyte
JAK-STAT and NF-kB pathways often dysregulated
CD274 (PD-1) and PDCDILG2 (PD-L2) gene amplification (Chromosome 9)
Clinical Presentation
Typically 20-30 year olds
Bulky anterior mediastinal mass +/- invasion of local structures
Compressive symptoms – effusions, SVCO
BM involvement / other extra-nodal disease is rare at diagnosis
Staging
PET-CT preferred
BM biopsy not mandatory if PET performed – advised if other extra-nodal disease present as result may change management (?CNS prophylaxis)
Treatment
Evidence base
Lack of prospective, randomised trials in PMBCL
PMBCL patients were included within the MInT Trial, and as for DLBCL the addition of rituximab to CHOP improved response rates and EFS.
Current frequently used regimens
R-CHOPx6 + ISRT
R-da-EPOCHx6 (radiotherapy-free)
Some of the R-CHOP vs R-da-EPOCH data:
NEJM 2013 - Ph2, single arm. 51 pts. R-da-EPOCH. 5yr EFS 93%, OS 97%
Blood 2020 - 69 pts, random., R-da-EPOCH vs R-CHOP. 5yr EFS 91% vs 64%. OS 98% vs 74%.
Blood Adv 2021 - Retrospect, 313 pts, R-CHOP-21 patients had 3yr PFS 87%, OS 87%
Blood 2022 - Retrospect, 122 pts, R-da-EPOCH, 3yr PFS 93%, OS 97%
Involved Site Radiotherapy (ISRT)
Currently given post R-CHOP to site of bulk disease
Ongoing IELSG 37 trial is looking at whether this can be omitted
CNS Prophylaxis
As per DLBCL. Most patients will have low IPI and not require CNS prophylaxis
Fertility & Pregnancy
Consider fertility preservation measures where clinical stability allows
Rates of infertility post R-CHOP are low
Diagnosis during pregnancy
R-CHOP has been given in 2nd and 3rd trimesters with successful outcomes
Avoid anti-metabolites
Insufficient data of R-da-EPOCH
PET-CT Response Assessment
When?
2-3 months post treatment for R-CHOP + ISRT
6 weeks post treatment for R-da-EPOCH
Outcomes in PMBCL correlate with the Lugano classification
Deauville Score 1-3: Complete Metabolic Response (CMR). Relapse very rare
Deauville Score 4: Probably inflammatory change. Some pts relapse
Deauville Score 5: Associated with a poor prognosis
Prognosis
50 PMBCL patients receiving R-CHOP within NCRI Gleeson et al 2016
5-yr PFS 80%, OS 84%
43 better risk PMBCL patients receiving R-CHOP within MInT trial 2011
3-yr EFS 78%, OS 88.5%
Relapse/Refractory Disease
10-30% of cases
Majority occur within 12 months, rare after 2 years
Extra-nodal sites commonly involved, but CNS and BM uncommon
Rx: Salvage followed by autograft as per DLBCL