Primary CNS Lymphoma: Treatment

Primary CNS Lymphoma: overview

This algorithm outlines treatment of primary CNS lymphoma in immunocompetent patients, organized into induction, consolidation and relapse. Induction is built on a high-dose methotrexate backbone, with the MATRix regimen (high-dose methotrexate, cytarabine, thiotepa and rituximab) shown on the chart.

For consolidation, thiotepa-based autologous stem cell transplant is the preferred option for fit patients and is noted on the chart as durable. Whole-brain radiotherapy is the alternative, flagged for its risk of neurotoxicity. For relapsed or refractory disease, the chart lists targeted therapy with ibrutinib or lenalidomide, or re-induction with high-dose methotrexate. The chart links only the MATRix regimen to a named study and gives no trial summaries for the consolidation or relapse branches.

Trials behind this algorithm

MATRix/IELSG43 trial Illerhaus G et al, Lancet, 2026; PMID: 42486133

Background reading: Primary CNS lymphoma (PCNSL) board review notes.

Primary CNS Lymphoma: the algorithm in words

Starting point: Primary CNS lymphoma (immunocompetent). Full background: Primary CNS lymphoma (PCNSL) notes.

Induction (first-line): HD-MTX backbone: MATRix (HD-MTX + cytarabine + thiotepa + rituximab) (MATRix).
Consolidation (first-line): Preferred (fit): Thiotepa-based autologous HSCT (durable); Alternative: Whole-brain RT (neurotoxicity risk).
Relapsed / refractory (second-line): Targeted: Ibrutinib / lenalidomide (or re-induction HD-MTX).