cancersCancer

Primary mediastinal (thymic) large B-cell lymphoma

aka PMBCL, PMBL, Primary mediastinal large B-cell lymphoma, Thymic large B-cell lymphoma, Mediastinal grey zone lymphoma (related)

Primary mediastinal B-cell lymphoma is a fast-growing lymphoma of the thymus behind the breastbone that mostly affects young women. Immunochemotherapy cures about nine in ten, radiotherapy can now be skipped when the end-of-treatment scan is clear, and PD-1 antibodies and CAR-T cells rescue many of those who relapse.

Part ofNon-Hodgkin lymphoma (all types)

Primary mediastinal large B-cell lymphoma is a distinct entity in the WHO classification, arising from thymic medullary B cells and sharing biology with nodular sclerosis classical Hodgkin lymphoma: gains and rearrangements of 9p24.1 (PD-L1, PD-L2, JAK2), CIITA rearrangements with loss of MHC class II, JAK-STAT and NF-kappa-B activation, and weak CD30 expression. It expresses CD20, CD23 and MAL, typically lacks surface immunoglobulin, and presents as a bulky anterior mediastinal mass in patients with a median age around 35, with local spread to lung, pleura and pericardium but rarely to marrow. Mediastinal grey zone lymphoma sits between it and Hodgkin lymphoma.

First-line treatment is rituximab-based immunochemotherapy. The National Cancer Institute series of dose-adjusted EPOCH-R (Dunleavy, NEJM 2013) treated 51 patients without radiotherapy with event-free survival of 93 percent and overall survival of 97 percent, and DA-EPOCH-R became the regimen that lets young patients avoid mediastinal radiotherapy; R-CHOP with consolidation radiotherapy is the alternative. The IELSG37 trial (2024) randomised patients in complete metabolic response on end-of-treatment PET to radiotherapy or observation and showed no loss of disease control without radiotherapy (30-month progression-free survival 96.7 versus 98.5 percent), so PET now decides who is irradiated and most patients are spared the heart and breast cancer risks of chest radiotherapy.

Relapsed or refractory disease, about 10 to 15 percent of patients, is treated with salvage chemotherapy and autologous transplant when chemosensitive, and the 9p24.1 lesion makes it one of the most immunotherapy-sensitive B-cell lymphomas: pembrolizumab produced a 45 percent response rate in KEYNOTE-170 and was approved in June 2018, the first drug licensed specifically for this lymphoma; nivolumab plus brentuximab vedotin gave a 73 percent response rate in CheckMate 436; and the CD19 CAR-T products axicabtagene ciloleucel and lisocabtagene maraleucel are licensed for large B-cell lymphoma including primary mediastinal disease. Open questions are how to identify the few patients who fail first-line therapy early, whether checkpoint blockade belongs in first line, and how to reduce the late effects of anthracycline and radiotherapy in survivors who are mostly in their thirties.

State of the art

DA-EPOCH-R cures about nine in ten patients without radiotherapy.
IELSG37 showed that radiotherapy can be omitted after a complete metabolic response on PET.
PD-1 blockade, alone or with brentuximab vedotin, rescues many relapsed patients because of the 9p24.1 lesion.
CD19 CAR-T labels for large B-cell lymphoma include this entity.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Cyclophosphamide Doxorubicin Etoposide Vincristine source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
Axicabtagene ciloleucel Lisocabtagene maraleucel source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Nivolumab Pembrolizumab source
Emergency services now
Skin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Brentuximab vedotin source
Check before combining
Food and drink: Doxorubicin
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
Doxorubicin source
Check before combining
Food and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Pembrolizumab source

See all on the product pages:Axicabtagene ciloleucel Brentuximab vedotin Cyclophosphamide Doxorubicin Etoposide Lisocabtagene maraleucel Nivolumab Pembrolizumab Vincristine·Printable cards in the navigator

Anatomy and lymph node drainage

Bone marrow, lymph nodes and spleen: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.

Subsites

Bone marrow (leukaemia, MDS, MPN, myeloma)Classic primary mediastinal B-cell lymphoma (young adults, anterior mediastinal mass, 9p24.1 gain) · Mediastinal grey zone lymphoma (features between primary mediastinal B-cell lymphoma and nodular sclerosis classical Hodgkin lymphoma) · Relapsed or refractory primary mediastinal B-cell lymphoma (PD-1 blockade, CAR-T, autologous transplant)
Lymph node germinal centre (lymphomas)Mediastinal grey zone lymphoma (features between primary mediastinal B-cell lymphoma and nodular sclerosis classical Hodgkin lymphoma)
Spleen
Blood (leukaemic phase)
Lytic bone lesions (myeloma)
Skin and extranodal sitesClassic primary mediastinal B-cell lymphoma (young adults, anterior mediastinal mass, 9p24.1 gain) · Mediastinal grey zone lymphoma (features between primary mediastinal B-cell lymphoma and nodular sclerosis classical Hodgkin lymphoma) · Relapsed or refractory primary mediastinal B-cell lymphoma (PD-1 blockade, CAR-T, autologous transplant)

Regional lymph nodes

cervical
axillary
mediastinal
para-aortic and mesenteric
inguinal

In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.

Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis

Who gets it and what has changed

About 2 to 4 percent of non-Hodgkin lymphomas, arising from thymic B cells in young adults, mostly women in their thirties, who present with a bulky anterior chest mass, cough, superior vena cava obstruction or breathlessness; most are cured with first-line immunochemotherapy.

Group

haematologic

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →1 regimens →Staging and risk scores →

Decisions you may face

3 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

First line8 Residual PET-positive disease after immunochemotherapy3 Relapsed or refractory7

First line

Dose-adjusted EPOCH-R for six cycles without radiotherapy, or R-CHOP for six cycles with PET-guided consolidation radiotherapy; end-of-treatment PET decides whether radiotherapy is needed (IELSG37).

NCCN Guidelines: B-Cell Lymphomas

RituximabDoxorubicinCyclophosphamideEtoposideVincristinePrednisoneR-CHOP (lymphoma chemoimmunotherapy)FDG PET PET-adapted (response-adapted) therapy IELSG37

Residual PET-positive disease after immunochemotherapy

Biopsy where feasible; involved-site radiotherapy to the mediastinum (30 to 36 Gy) for persistent uptake; salvage therapy for proven refractory disease.

NCCN Guidelines: B-Cell Lymphomas

IMRT / IGRT (modern external beam)Proton therapy FDG PET Deauville five-point scale

Relapsed or refractory

Salvage chemotherapy then autologous stem cell transplant if chemosensitive; pembrolizumab (KEYNOTE-170) or nivolumab plus brentuximab vedotin; CD19 CAR-T (axicabtagene ciloleucel, lisocabtagene maraleucel) after two lines or as second line for early relapse.

NCCN Guidelines: B-Cell Lymphomas

Autologous stem cell transplant (high-dose therapy)PembrolizumabKEYNOTE-170NivolumabBrentuximab vedotinAxicabtagene ciloleucelLisocabtagene maraleucelCAR-T cell therapy

Subtypes & biomarkers

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Subtypes

Classic primary mediastinal B-cell lymphoma (young adults, anterior mediastinal mass, 9p24.1 gain)
Mediastinal grey zone lymphoma (features between primary mediastinal B-cell lymphoma and nodular sclerosis classical Hodgkin lymphoma)
Relapsed or refractory primary mediastinal B-cell lymphoma (PD-1 blockade, CAR-T, autologous transplant)

Biomarkers clinicians test

CD20, CD23, MAL and weak or partial CD30 expression
9p24.1 gain or amplification (PD-L1, PD-L2, JAK2)
CIITA rearrangement and loss of MHC class II
End-of-treatment FDG PET (Deauville score) to decide on radiotherapy
Circulating tumour DNA for response monitoring (under study)

How often this target appears

History

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1980Mediastinal large B-cell lymphoma of thymic origin first described as a distinct clinical entity
2001WHO classification lists primary mediastinal large B-cell lymphoma as a separate entity
Non-Hodgkin lymphoma (all types)
2003Gene expression profiling shows its kinship with classical Hodgkin lymphoma and the 9p24.1 lesion
Hodgkin lymphoma PD-L1 JAK2
2013Dunleavy: dose-adjusted EPOCH-R cures 93 percent without radiotherapy (NEJM)
RituximabEtoposideDoxorubicinWyndham H. Wilson
2017Axicabtagene ciloleucel approved for large B-cell lymphoma, including primary mediastinal disease
Axicabtagene ciloleucelCAR-T cell therapy
2018Pembrolizumab approved for relapsed or refractory disease after KEYNOTE-170
PembrolizumabKEYNOTE-170
2019CheckMate 436: nivolumab plus brentuximab vedotin, 73 percent response rate
NivolumabBrentuximab vedotin
2024IELSG37: radiotherapy can be omitted after complete metabolic response
IELSG37 PET-adapted (response-adapted) therapy

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 13 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Primary mediastinal (thymic) large B-cell lymphoma, drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Technologies being tested · 1

ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)

Trials reported · 2

IELSG37 · phase 3 · 2024 · positive
KEYNOTE-170 · phase 2 · 2019 · positive

Open problems and what is being done

No validated way to identify the 10 to 15 percent who will fail first-line therapy before they do.
Checkpoint blockade in first line is untested in randomised trials.
Late cardiac and second-cancer effects of anthracyclines and radiotherapy fall on patients in their thirties.
Grey zone lymphoma has no trial-defined standard.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Primary mediastinal (thymic) large B-cell lymphoma

condition: Primary mediastinal large B-cell lymphoma

Open on ClinicalTrials.gov →

within

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Landmark trials

IELSG37 KEYNOTE-170 TRANSFORM ZUMA-7

Expert centres

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Where the expertise is

Expert centres

195 centres in 45 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

195 centres


Memorial Sloan Kettering Cancer Center New York · cancer center	United States	NCI comprehensive	5,100	94,456	Comprehensive genomic profiling CAR-T cell therapy Digital pathology & AI	#1
MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital	South Korea	none recorded	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
Dana-Farber Brigham Cancer Center Boston · cancer center	United States	NCI comprehensive	4,335	73,845	none recorded	#15
Massachusetts General Hospital Cancer Center Boston · hospital	United States	NCI comprehensive	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Heidelberg University Hospital / NCT / DKFZ Heidelberg · cancer center	Germany	none recorded	3,456	45,745	FAPI PET Targeted alpha therapy Carbon-ion therapy DNA methylation profiling +5	#18
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Institut Curie Paris · cancer center	France	none recorded	1,065	15,111	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	#21
The Christie NHS Foundation Trust Manchester · cancer center	United Kingdom	none recorded	104	2,145	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems MR-guided adaptive radiotherapy TomoTherapy and Radixact (helical radiotherapy)	#23
Stanford Health Care / Stanford Cancer Institute Stanford · university	United States	NCI comprehensive	3,000	50,162	CAR-T cell therapy SBRT / SABR (stereotactic radiotherapy)CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)+1	#30
Fudan University Shanghai Cancer Center Shanghai · cancer center	China	none recorded	1,678	18,354	TROP2 PET Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Carbon-ion therapy +1	#55
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences Tianjin · hospital	China	none recorded	4,959	62,355	CAR-T cell therapy	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Primary mediastinal (thymic) large B-cell lymphoma but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Primary mediastinal (thymic) large B-cell lymphoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 16 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example CD20, CD23, MAL and weak or partial CD30 expression, 9p24.1 gain or amplification, CIITA rearrangement and loss of MHC class II, End-of-treatment FDG PETto decide on radiotherapy, Circulating tumour DNA for response monitoring), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Classic primary mediastinal B-cell lymphoma, Mediastinal grey zone lymphoma, Relapsed or refractory primary mediastinal B-cell lymphoma.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

First line

For my situation (first line), which of the standard options do you recommend and why?
Why: Guideline options include: Dose-adjusted EPOCH-R for six cycles without radiotherapy, or R-CHOP for six cycles with PET-guided consolidation radiotherapy; end-of-treatment PET decides whether radiotherapy is needed (IELSG37).
Am I a candidate for Rituximab, Doxorubicin, Cyclophosphamide or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of IELSG37 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Residual PET-positive disease after immunochemotherapy

For my situation (residual pet-positive disease after immunochemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Biopsy where feasible; involved-site radiotherapy to the mediastinum (30 to 36 Gy) for persistent uptake; salvage therapy for proven refractory disease.

Relapsed or refractory

For my situation (relapsed or refractory), which of the standard options do you recommend and why?
Why: Guideline options include: Salvage chemotherapy then autologous stem cell transplant if chemosensitive; pembrolizumab (KEYNOTE-170) or nivolumab plus brentuximab vedotin; CD19 CAR-T (axicabtagene ciloleucel, lisocabtagene maraleucel) after two lines or as second line for early relapse.
Am I a candidate for Pembrolizumab, Nivolumab, Brentuximab vedotin or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-170 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

Are there clinical trials I could join, for example of IELSG37, KEYNOTE-170, ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ), Glofitamab?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “No validated way to identify the 10 to 15 percent who will fail first-line therapy before they do”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Checkpoint blockade in first line is untested in randomised trials”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.