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)

  • Data for R-CHOP better established. No trials comparing the two.

 

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