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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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). | not mapped |
| 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. | not mapped |
| 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. | not mapped |
| Primary mediastinal B-cell lymphoma: which first-line regimen, and why radiotherapy is now usually avoided | A disease of young adults, more often women, presenting with a bulky mass between the lungs that can compress the superior vena cava. It is biologically closer to Hodgkin lymphoma than to diffuse large B-cell lymphoma, which is why PD-1 blockade works in it. Dose-adjusted EPOCH-R for six cycles is the regimen most used in the United States, on the strength of a National Cancer Institute series in which five-year event-free survival was 93 per cent and overall survival 97 per cent, with radiotherapy avoided in 96 per cent of patients. R-CHOP with consolidation radiotherapy is the alternative used in much of Europe. There has never been a randomised comparison of the two. What has been settled is the radiotherapy. IELSG37 randomised patients with a negative end-of-treatment PET to mediastinal radiotherapy or observation: 30-month progression-free survival was 96.2 per cent with observation against 98.5 per cent with radiotherapy, non-inferior, and overall survival was 99 per cent in both arms. Since the patients are young and the field sits over the heart and breasts, avoiding it matters for the next forty years. Radiotherapy is still given where the end-of-treatment PET is positive. | not mapped |
| Primary mediastinal B-cell lymphoma that relapses or does not respond | Relapse is uncommon and almost always early, within the first year. CD19 CAR-T is the treatment of choice and primary mediastinal disease was included in the pivotal ZUMA-1 and TRANSCEND populations. Where CAR-T is not available or has failed, pembrolizumab has an established role: KEYNOTE-170 treated 53 patients whose disease had relapsed after autologous transplant or who could not have one after two or more lines, and reported an objective response of 45 per cent and complete response of 13 per cent, which led to accelerated approval in the United States on 13 June 2018, converted to traditional approval on 14 October 2020. Nivolumab with brentuximab vedotin is the other checkpoint-based option. Salvage chemotherapy with autologous transplant is used where the disease is still chemosensitive and CAR-T is not accessible. Mediastinal radiotherapy is added to a residual localised site. | not mapped |