{"entity":{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"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)"],"tldr":"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.","summary":"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.\n\nFirst-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.\n\nRelapsed 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Primary_mediastinal_B-cell_lymphoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Primary_mediastinal_B-cell_lymphoma"},{"label":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":["fdg-pet","pet-adapted-therapy","checkpoint-inhibitor","car-t","autologous-stem-cell-transplant","adc","imrt-igrt","ctdna-lymphoma-monitoring"],"targets":["cd20","cd30","cd19","pd1","pdl1","jak2","cd79b"],"drugs":["rituximab","doxorubicin","cyclophosphamide","etoposide","vincristine","prednisone","pembrolizumab","nivolumab","brentuximab-vedotin","axicabtagene-ciloleucel","lisocabtagene-maraleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","lugano-classification","deauville-score","autologous-transplant","crs","icans"],"trials":["keynote-170","ielsg37","zuma-7","transform"],"people":["wyndham-wilson"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"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.","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":["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)"],"standardOfCare":[{"setting":"First line","approach":"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).","refs":["rituximab","doxorubicin","cyclophosphamide","etoposide","vincristine","prednisone","r-chop","fdg-pet","pet-adapted-therapy","ielsg37"],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Residual PET-positive disease after immunochemotherapy","approach":"Biopsy where feasible; involved-site radiotherapy to the mediastinum (30 to 36 Gy) for persistent uptake; salvage therapy for proven refractory disease.","refs":["imrt-igrt","proton-therapy","fdg-pet","deauville-score"],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Relapsed or refractory","approach":"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.","refs":["autologous-stem-cell-transplant","pembrolizumab","keynote-170","nivolumab","brentuximab-vedotin","axicabtagene-ciloleucel","lisocabtagene-maraleucel","car-t"],"guideline":{"version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}}],"stateOfArt":["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."],"history":[{"year":1980,"title":"Mediastinal large B-cell lymphoma of thymic origin first described as a distinct clinical entity","refs":[]},{"year":2001,"title":"WHO classification lists primary mediastinal large B-cell lymphoma as a separate entity","refs":["non-hodgkin-lymphoma"]},{"year":2003,"title":"Gene expression profiling shows its kinship with classical Hodgkin lymphoma and the 9p24.1 lesion","refs":["hodgkin-lymphoma","pdl1","jak2"]},{"year":2013,"title":"Dunleavy: dose-adjusted EPOCH-R cures 93 percent without radiotherapy (NEJM)","refs":["rituximab","etoposide","doxorubicin","wyndham-wilson"]},{"year":2017,"title":"Axicabtagene ciloleucel approved for large B-cell lymphoma, including primary mediastinal disease","refs":["axicabtagene-ciloleucel","car-t"]},{"year":2018,"title":"Pembrolizumab approved for relapsed or refractory disease after KEYNOTE-170","refs":["pembrolizumab","keynote-170"]},{"year":2019,"title":"CheckMate 436: nivolumab plus brentuximab vedotin, 73 percent response rate","refs":["nivolumab","brentuximab-vedotin"]},{"year":2024,"title":"IELSG37: radiotherapy can be omitted after complete metabolic response","refs":["ielsg37","pet-adapted-therapy"]}],"pipeline":["ielsg37","keynote-170","ctdna-lymphoma-monitoring","glofitamab","epcoritamab","lisocabtagene-maraleucel"],"openProblems":["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."],"parent":"non-hodgkin-lymphoma"},"route":"/cancers/primary-mediastinal-b-cell-lymphoma/","neighbours":{"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"ctdna-lymphoma-monitoring","kind":"technology","name":"ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)","route":"/technologies/ctdna-lymphoma-monitoring/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"pet-adapted-therapy","kind":"technology","name":"PET-adapted (response-adapted) therapy","route":"/technologies/pet-adapted-therapy/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"target":[{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"cd79b","kind":"target","name":"CD79b","route":"/targets/cd79b/"},{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"epcoritamab","kind":"drug","name":"Epcoritamab","route":"/drugs/epcoritamab/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"glofitamab","kind":"drug","name":"Glofitamab","route":"/drugs/glofitamab/"},{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"autologous-transplant","kind":"term","name":"Autologous stem cell transplant (ASCT)","route":"/terms/autologous-transplant/"},{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"deauville-score","kind":"term","name":"Deauville five-point scale","route":"/terms/deauville-score/"},{"id":"icans","kind":"term","name":"ICANS (neurotoxicity)","route":"/terms/icans/"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","route":"/terms/lugano-classification/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"}],"trial":[{"id":"ielsg37","kind":"trial","name":"IELSG37","route":"/trials/ielsg37/"},{"id":"keynote-170","kind":"trial","name":"KEYNOTE-170","route":"/trials/keynote-170/"},{"id":"transform","kind":"trial","name":"TRANSFORM","route":"/trials/transform/"},{"id":"zuma-7","kind":"trial","name":"ZUMA-7","route":"/trials/zuma-7/"}],"person":[{"id":"wyndham-wilson","kind":"person","name":"Wyndham H. Wilson","route":"/people/wyndham-wilson/"}],"cancer":[{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}]}}