Primary Mediastinal B-Cell Lymphoma (PMBCL) (BSH 2026)

 

Epidemiology

2-4% of all Non-Hodgkin lymphomas

Typically 20-40 year olds

Female > Male

Pathology

Genetically distinct from DLBCL

Some overlap with classical Hodgkin lymphoma (>80% cases CD30+)

Cell of origin: Germinal centre or post-germinal centre thymic B lymphocyte

Typical Immunophenotype

  • CD45+

  • CD30+ (weak compared to Hodgkins)

  • Positive for B-cell antigens - CD19, CD20, CD22 and CD7a

  • Positive for transcription factors - BOB1, OCT2, PAX5

  • Positive IRF4, CD23

  • Variable BCL6, BCL2, occasionally CD10, occasionally CD15

  • Negative EBER

Molecular/Cytogenetics

  • JAK-STAT and NF-kB pathways often dysregulated

  • Re-arrangements usually specific for PMBCL include:

    • PDL1 (CD274) and PDL2 (PDCD1LG2) rearrangements or copy number abnormal.

    • CIITA rearrangements, REL amiplification

  • Common pathogenic variants on NGS include:

    • SOCS1, GNA13, STAT6, CD58, B2M, ITPKB, NFKBIE, TNFAIP3, IL4R 

Clinical Presentation

 

Bulky anterior mediastinal mass +/- invasion of local structures

PE reported in ~30% patients (retrospective data)

Compressive symptoms – effusions, SVCO

BM involvement / other extra-nodal disease is rare at diagnosis

 

Staging

Imaging - PET-CT preferred

Bone marrow staging - not mandatory if PET performed

 

Fertility & Pregnancy

 

Consider fertility preservation measures where clinical stability allows

Rates of infertility post R-CHOP are low, but ovarian failure can occur particularly if >40yo

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

Treatment

 

Evidence base

  • Lack of prospective, randomised trials in PMBCL

  • Available pooled data indicates R-CHOP21 is inferior to more intensive regimens

  • R-da-EPOCH now widely used on basis of positive phase 2 data

  • Key trials include:

    • IELSG37 2025 - Post-hoc analysis of IELSG37 chemo regimens (which had been chosen according to local practice). R-CHOP21 increased the risk of additional treatment due to higher rate of D5 on EoT PET. No statistically significant difference in PFS or OS compared to other regimens.

    • IELSG37 2024 - 545 patients. Randomised patients in CMR to RT vs observation. No difference in outcomes. RT can be omitted for D1-3 patients.

    • 2024 meta-analysis - 4000 patients from retrospective and early phase trials suggests benefit for dose-intensive regimens as compared to R-CHOP21

    • Wilson et al 2018 - D4-5 EoT PET does not accurately predict treatment failure

Supportive Care

  • Prophylactic-dose anticoagulation for all patients due to high thrombosis rate

  • Routine supportive medications as per relevant chemotherapy regimen

Current recommended UK 1st line Treatment

  • Clinical trial where available

  • R-da-EPOCHx6 (radiotherapy-free)

  • R-CHOP14 x6

  • (R-CHOP21 is not recommended)

 

Involved Site Radiotherapy (ISRT)

  • End of Treatment PET-CT guided decision-making

    • Deauville 1-3: Complete metabolic response. Omit radiotherapy.

    • Deauville 4: May represent residual inflammation. Optimum treatment is controversial. Re-biopsy if feasible. Radiotherapy or interval repeat PET-CT are valid options. Patient-by-patient basis.

    • Deauville 5: Poorer prognostic indicator, more likely to represent lymphoma. Re-biopsy if feasible. Consider whether radiotherapy vs second line chemotherapy is appropriate on patient-by-patient basis.

CNS Prophylaxis

  •  As per DLBCL. Most patients will have low IPI and not require CNS prophylaxis

 

PET-CT Response Assessment

When?

  • Interim assessment mid-treatment (timing as per local policies)

  • 6 weeks post Day 1 of Cycle 6 R-da-EPOCH

  • 3 months post radiotherapy (if administered)

 

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

  • Also see above notes on consolidation radiotherapy

 

Prognosis (from IELSG37 trial)

 

If CMR after R-da-EPOCH x6: 30-month PFS 96-98%, 5-yr OS 99%

DS4 on EoT PET: 30-month PFS 95% (Note: 86% patients received radiotherapy)

DS5 on EoT PET: 5-yr PFS 60%, 5-yr OS 74%

 

Relapse/Refractory Disease

 

10-30% of cases

Majority occur within 12 months, rare after 2 years

Outcomes are worse than for relapsed DLBCL

Extra-nodal sites commonly involved, but CNS and BM uncommon

Rx: As per DLBCL pathways - CAR-T / Autograft / Bi-specifics / Chemotherapy as tolerated/available

See 2026 guideline for details