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Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma

Wendler, Julia; Fox, Christopher P.; Valk, Elke; Steinheber, Cora; Fricker, Heidi; Isbell, Lisa K.; Neumaier, Simone; Okosun, Jessica; Scherer, Florian; Ihorst, Gabriele; Cwynarski, Kate; Schorb, Elisabeth; Illerhaus, Gerald

Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma Thumbnail


Julia Wendler

Clinical Professor in Haematology

Elke Valk

Cora Steinheber

Heidi Fricker

Lisa K. Isbell

Simone Neumaier

Jessica Okosun

Florian Scherer

Gabriele Ihorst

Kate Cwynarski

Elisabeth Schorb

Gerald Illerhaus


Background: Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT. Methods: This is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months. Discussion: Current treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy. Trial registration: German clinical trials registry DRKS00022768 registered June 10th, 2021.


Wendler, J., Fox, C. P., Valk, E., Steinheber, C., Fricker, H., Isbell, L. K., …Illerhaus, G. (2022). Optimizing MATRix as remission induction in PCNSL: de-escalated induction treatment in newly diagnosed primary CNS lymphoma. BMC Cancer, 22(1), Article 971.

Journal Article Type Article
Acceptance Date May 31, 2022
Online Publication Date Sep 10, 2022
Publication Date Dec 1, 2022
Deposit Date Jan 11, 2023
Publicly Available Date Jan 11, 2023
Journal BMC Cancer
Electronic ISSN 1471-2407
Peer Reviewed Peer Reviewed
Volume 22
Issue 1
Article Number 971
Keywords Cancer Research; Genetics; Oncology
Public URL
Publisher URL


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