Skip to main content

Research Repository

Advanced Search

Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial

Ferreri, Andrés J. M.; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P.; Schorb, Elisabeth; Celico, Claudia; Falautano, Monica; Nonis, Alessandro; La Rosée, Paul; Binder, Mascia; Fabbri, Alberto; Ilariucci, Fiorella; Krampera, Mauro; Roth, Alexander; Hemmaway, Claire; Johnson, Peter W.; Linton, Kim M.; Pukrop, Tobias; Gørløv, Jettes Sønderskov; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jense; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Zanni, Manuela; Krause, Stefan W.; Schmoll, Hans J.; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Thurner, Lorenz; Cabras, Giuseppina; Pennese, Elsa; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S.; Finke, Jurgen; Ferranti, Antonella; Cozens, Kelly; Burger, Elvira; Ielmini, Nicoletta; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald; IELSG32 study investigators

Authors

Andrés J. M. Ferreri

Kate Cwynarski

Elisa Pulczynski

CHRIS FOX Christopher.Fox@nottingham.ac.uk
Clinical Professor in Haematology

Elisabeth Schorb

Claudia Celico

Monica Falautano

Alessandro Nonis

Paul La Rosée

Mascia Binder

Alberto Fabbri

Fiorella Ilariucci

Mauro Krampera

Alexander Roth

Claire Hemmaway

Peter W. Johnson

Kim M. Linton

Tobias Pukrop

Jettes Sønderskov Gørløv

Monica Balzarotti

Georg Hess

Ulrich Keller

Stephan Stilgenbauer

Jense Panse

Alessandra Tucci

Lorella Orsucci

Francesco Pisani

Manuela Zanni

Stefan W. Krause

Hans J. Schmoll

Bernd Hertenstein

Mathias Rummel

Jeffery Smith

Lorenz Thurner

Giuseppina Cabras

Elsa Pennese

Maurilio Ponzoni

Martina Deckert

Letterio S. Politi

Jurgen Finke

Antonella Ferranti

Kelly Cozens

Elvira Burger

Nicoletta Ielmini

Franco Cavalli

Emanuele Zucca

Gerald Illerhaus

IELSG32 study investigators



Abstract

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.

Journal Article Type Article
Acceptance Date Apr 20, 2022
Online Publication Date May 13, 2022
Publication Date 2022-07
Deposit Date Jan 11, 2023
Journal Leukemia
Print ISSN 0887-6924
Electronic ISSN 1476-5551
Peer Reviewed Peer Reviewed
Volume 36
Issue 7
Pages 1870-1878
DOI https://doi.org/10.1038/s41375-022-01582-5
Public URL https://nottingham-repository.worktribe.com/output/15933268
Publisher URL https://www.nature.com/articles/s41375-022-01582-5