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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.
Peripheral T-cell lymphomas are lymphomas of T cells rather than B cells. They are rarer, more varied and, apart from a few subtypes, harder to treat than B-cell lymphomas; several new drugs help only defined subtypes.
PTCLs are a heterogeneous group: PTCL-NOS, nodal T-follicular-helper lymphomas (angioimmunoblastic), ALK-positive and ALK-negative anaplastic large-cell lymphoma (ALCL), adult T-cell leukaemia/lymphoma (HTLV-1), extranodal NK/T-cell lymphoma (EBV), enteropathy-associated and hepatosplenic T-cell lymphoma, and the cutaneous T-cell lymphomas (mycosis fungoides, Sézary syndrome). Except ALK-positive ALCL, five-year survival with CHOP is 30-40%.
CHOP or CHOEP remains the backbone; brentuximab vedotin-CHP replaced CHOP for CD30-positive PTCL after ECHELON-2 (2018) and is the standard for ALCL. Autologous transplant consolidation in first remission is common practice without randomised proof. Relapsed disease is treated with pralatrexate (2009), the HDAC inhibitors romidepsin (2009, US PTCL indication withdrawn 2021) and belinostat (2014), brentuximab, or allogeneic transplant. NK/T-cell lymphoma uses asparaginase-based regimens (SMILE, P-GemOx) and radiotherapy; PD-1 blockade is active. Cutaneous T-cell lymphoma is managed by skin-directed therapy, then mogamulizumab (anti-CCR4, MAVORIC 2018), brentuximab (ALCANZA), bexarotene, extracorporeal photopheresis, and allogeneic transplant.
| Setting | Approach | Guideline |
|---|---|---|
| First line, CD30+ PTCL / ALCL | Brentuximab vedotin + CHP ×6 (ECHELON-2, OS benefit) ± consolidative autologous transplant. | NCCN Category 1 (ALCL), ESMO-MCBS 4 |
| First line, other nodal PTCL | CHOP or CHOEP (≤60 years) ×6, autologous transplant consolidation in responders; clinical trial preferred. | NCCN Category 2A |
| Relapsed/refractory PTCL | Pralatrexate, belinostat, romidepsin (ex-US), brentuximab (CD30+), gemcitabine-based regimens, allogeneic HSCT for fit responders. | NCCN Category 2A |
| Mycosis fungoides / Sézary | Skin-directed therapy (topical steroids, phototherapy, radiotherapy, total-skin electron beam), then mogamulizumab (MAVORIC), brentuximab (ALCANZA, CD30+), bexarotene, interferon, photopheresis; allogeneic HSCT for advanced disease. | NCCN Category 1 (mogamulizumab, brentuximab) |
| Extranodal NK/T-cell | Asparaginase-based chemotherapy (P-GemOx, SMILE) with involved-site radiotherapy for localised disease; PD-1 inhibitors at relapse. | not mapped |
| Peripheral T-cell lymphoma: the questions that decide the regimen | Four things to establish before treatment. Which entity: ALK-positive anaplastic large cell lymphoma does much better than every other nodal T-cell lymphoma and is curable with chemotherapy alone in most patients; ALK-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified and the enteropathy-associated forms do considerably worse. CD30 expression by immunohistochemistry, because it decides whether brentuximab vedotin is added to first-line chemotherapy. Whether the disease is nodal, extranodal (nasal NK/T-cell), leukaemic (adult T-cell leukaemia/lymphoma, T-cell prolymphocytic leukaemia) or cutaneous, because those four groups have entirely different treatments. HTLV-1 serology where the patient comes from or has family from Japan, the Caribbean, west Africa, Iran or parts of South America, because adult T-cell leukaemia/lymphoma is treated differently from everything else. A breast implant-associated anaplastic large cell lymphoma presenting as a late seroma around an implant is treated primarily by complete surgical removal of the implant and capsule, and most patients need nothing else. That is a different disease from systemic anaplastic large cell lymphoma despite the shared name. | not mapped |
| First-line nodal peripheral T-cell lymphoma, CD30-positive: brentuximab vedotin with CHP | ECHELON-2 randomised 452 patients with untreated CD30-positive peripheral T-cell lymphoma to brentuximab vedotin with cyclophosphamide, doxorubicin and prednisone (A+CHP) or to CHOP. Median progression-free survival by blinded independent review was 48.2 against 20.8 months (hazard ratio 0.71), with improved overall survival, and toxicity was comparable: febrile neutropenia 18 against 15 per cent and peripheral neuropathy 52 against 55 per cent. It is the only positive randomised first-line trial in this family in twenty years and it changed the standard. Three-quarters of the trial population had systemic anaplastic large cell lymphoma, so the benefit is best established there and is extrapolated to other CD30-positive entities. Six cycles are given, with G-CSF support. Vincristine is omitted because brentuximab vedotin is itself a tubulin-directed agent and giving both causes unacceptable neuropathy. | NCCN Category 1 (A+CHP, CD30-positive) |
| First-line nodal peripheral T-cell lymphoma, CD30-negative: CHOP, CHOEP and an honest account of the evidence | CHOP for six cycles is the default, and it is a default rather than a demonstrated best. No randomised trial has shown any regimen superior to CHOP in CD30-negative nodal peripheral T-cell lymphoma, and roughly half of patients are not cured by it. Adding etoposide (CHOEP) is standard in much of Europe for patients under 60 with a normal LDH, on the basis of a retrospective analysis of the German High-Grade Non-Hodgkin Lymphoma Study Group trials in which that subgroup had better event-free survival; the analysis was not randomised and not confined to T-cell lymphoma, so the practice rests on an observation rather than a trial. Adding romidepsin to CHOP was tested properly in the Ro-CHOP trial and failed, which is why the United States withdrew romidepsin's peripheral T-cell lymphoma indication. Angioimmunoblastic T-cell lymphoma is the entity in which the epigenetic drugs look most promising, because it is driven by mutations in TET2, DNMT3A, IDH2 and RHOA; azacitidine-containing combinations and histone deacetylase inhibitors are being tested and are not yet standard. Enteropathy-associated T-cell lymphoma is treated with intensive regimens and early nutritional support, because it presents with perforation or obstruction in a malnourished patient with coeliac disease. Entering a trial is a reasonable first choice rather than a last resort in this group. | not mapped |