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IELSG32 built the MATRix regimen that is now the standard first treatment for lymphoma confined to the brain: adding rituximab and thiotepa to methotrexate and cytarabine doubled the complete remission rate, and its second part showed that a stem cell transplant works as well as whole-brain radiotherapy for consolidation, with less harm to thinking.
IELSG32 was an international randomised phase 2 trial in 227 patients with newly diagnosed primary CNS lymphoma. The first randomisation compared four courses of high-dose methotrexate and cytarabine alone (arm A), with rituximab (arm B), or with rituximab and thiotepa (arm C, the MATRix regimen). Patients with responsive or stable disease were then randomised to whole-brain radiotherapy of 36 Gy or high-dose carmustine and thiotepa with autologous stem cell transplant.
Complete remission after induction was 49 percent with MATRix against 23 percent with methotrexate-cytarabine alone and 30 percent with rituximab added, with more grade 4 haematological toxicity but similar infections; 6 percent of patients died of toxicity. In the second randomisation two-year failure-free survival was 76 percent after radiotherapy and 75 percent after transplant, with cognitive function preserved after transplant and impaired attention and executive function after radiotherapy. The corpus's primary CNS lymphoma page cites IELSG32 for thiotepa-based chemotherapy with autologous transplant.
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.
227 enrolled.
95% CI 38 to 60; 219 of 227 assessable across the three arms · 95% CI 21 to 42 · 95% CI 14 to 31
Source95% CI 65 to 87 · 95% CI 64 to 86
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Complete remission after induction chemotherapyprimary | MATRix: methotrexate, cytarabine, thiotepa, rituximab | - | 49% | - | - | link |
| Methotrexate + cytarabine + rituximab | - | 30% | ||||
| Methotrexate + cytarabine | - | 23% | ||||
| Failure-free survival at 2 years after the second randomisationprimary | Whole-brain radiotherapy 36 Gy with or without 9 Gy boost | - | 76% | - | - | link |
| Carmustine-thiotepa conditioning and autologous stem cell transplant | - | 75% | ||||
| Deaths from toxicity during induction | All induction arms | 219 | 6% | - | - | link |
Autologous transplant is an effective consolidation that avoids the neurotoxicity of whole-brain radiotherapy, and IELSG43 later showed it beats non-myeloablative consolidation.
MATRix became the reference induction for fit patients with primary CNS lymphoma and the control arm of later randomised trials.
Shares Carmustine, Cytarabine, Autologous stem cell transplant (high-dose therapy), Non-Hodgkin lymphoma (all types) and the tag soc-trials.
Shares Thiotepa, Autologous stem cell transplant (high-dose therapy), Brain and spinal cord tumours (all types), Methotrexate and the tag soc-trials.
Shares Thiotepa, Autologous stem cell transplant (high-dose therapy), Brain and spinal cord tumours (all types), Cytotoxic chemotherapy and the tag soc-trials.
Shares Cytarabine, Autologous stem cell transplant (high-dose therapy), Rituximab, 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 soc-trials.
Shares Rituximab, 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), Cytotoxic chemotherapy and the tag soc-trials.
Shares Rituximab, 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), Cytotoxic chemotherapy and the tag soc-trials.
Shares Rituximab, Non-Hodgkin lymphoma (all types), Cytotoxic chemotherapy and the tag soc-trials.
Shares Brain and spinal cord tumours (all types), Cytotoxic chemotherapy and the tag soc-trials.