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An asparaginase-based regimen gave a response in four out of five people with an aggressive nasal lymphoma that had always resisted standard chemotherapy, and nearly all of them had dangerously low white cell counts.
Extranodal natural killer/T-cell lymphoma, nasal type, is driven by Epstein-Barr virus and is concentrated in east Asia and Latin America. Anthracycline-based regimens such as CHOP fail in it, and every regimen that works is built on asparaginase. The explanation usually given is that the tumour expresses P-glycoprotein, a pump that expels anthracyclines but not asparaginase; immunohistochemical expression has been documented (Wang, American Journal of Hematology 2008), but a Korean series found no correlation between P-glycoprotein and chemotherapy resistance (Kim, Leukemia and Lymphoma 2004), so the mechanism is the accepted account rather than a settled one.
The NK-Cell Tumor Study Group tested SMILE, a five-drug regimen of dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide, in 38 eligible patients with newly diagnosed stage IV, relapsed or refractory disease. The first two patients died of infection, after which eligibility was tightened to require a lymphocyte count of 500 per microlitre or more, and no further treatment-related deaths occurred. After two cycles the overall response rate was 79 per cent (90 per cent confidence interval 65 to 89) and the complete response rate 45 per cent. Of the 28 patients who completed the protocol treatment, 19 went on to haematopoietic stem-cell transplantation. One-year overall survival was 55 per cent (95 per cent confidence interval 38 to 69).
Grade 4 neutropenia occurred in 92 per cent and grade 3 or 4 infection in 61 per cent. SMILE is therefore a regimen for a patient who can be supported through profound myelosuppression, and the eligibility amendment is part of the result rather than a footnote to it. The disease has no cancer record of its own in OnCo yet; it is attached here to peripheral T-cell lymphoma.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
38 analysed.
90 per cent confidence interval 65 to 89
Source95 per cent confidence interval 38 to 69
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall response rate after two cyclesprimary | SMILE | 38 | 79% | - | - | link |
| Overall survival at 1 year | SMILE | 38 | 55% | - | - | - |
Shares ECHELON-2, Complete response, Randomised evidence for the T-cell lymphomas, including the ones that are not in Europe or North America, Etoposide and the tag lymphoma-evidence.
Shares Complete response, Randomised evidence for the T-cell lymphomas, including the ones that are not in Europe or North America, Etoposide, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma) and the tag lymphoma-evidence.
Shares Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study, Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase), Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Most of the world has almost no cancer care and the tag lymphoma-evidence.
Shares Autologous stem cell transplant (ASCT), Methotrexate, Rare and paediatric cancers without markets, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Non-Hodgkin lymphoma (all types) and the tag lymphoma-evidence.
Shares Rare and paediatric cancers without markets, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Most of the world has almost no cancer care, Non-Hodgkin lymphoma (all types) and the tag lymphoma-evidence.
Shares Complete response, Objective response rate (ORR), Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Non-Hodgkin lymphoma (all types) and the tag lymphoma-evidence.