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 AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, Celico C, Falautano M, Nonis A, La Rosee P, Binder M, Fabbri A, Ilariucci F, Krampera M, Roth A, Hemmaway C, Johnson PW, Linton KM, Pukrop T, Gorlov JS, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Zanni M, Krause S, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Thurner L, Cabras G, Pennese E, Ponzoni M, Deckert M, Politi LS, Finke J, Ferranti A, Cozens K, Burger E, Ielmini N, Cavalli F, Zucca E, Illerhaus G (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1038/s41375-022-01582-5

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Aintree University Hospital United Kingdom (GB) Università Vita-Salute San Raffaele (UniSR) Italy (IT) Ospedale Civile Santo Spirito Italy (IT) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Fondazione Italiana Linfomi Onlus, Foundation Italiana Linfomi Italy (IT) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Italy (IT) International Extranodal Lymphoma Study Group (IELSG) Switzerland (CH) University College Hospital United Kingdom (GB) Arcispedale Santa Maria Nuova Italy (IT) Rigshospitalet Denmark (DK) Aarhus University Hospital / Aarhus Universitetshospital Denmark (DK) Christie NHS Foundation Trust United Kingdom (GB) Universitätsklinikum Essen Germany (DE) Nottingham University Hospitals United Kingdom (GB) Istituto Clinico Humanitas Italy (IT) University of Southampton United Kingdom (GB) Queen's Hospital United Kingdom (GB) Klinikum Stuttgart Germany (DE) University Hospital Siena Italy (IT) Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Italy (IT) Universität Ulm Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) Azienda Ospedaliera Nazionale SS.Antonio e Biagio e C.Arrigo Italy (IT) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) University of Verona / Università degli Studi di Verona Italy (IT) University Hospital Southampton NHS United Kingdom (GB) Schwarzwald-Baar Klinikum Germany (DE) Technische Universität München (TUM) Germany (DE) Georg-August-Universität Göttingen Germany (DE) Istituto Nazionale Tumori Regina Elena (IRE) Italy (IT)

How to cite

APA:

Ferreri, A.J.M., Cwynarski, K., Pulczynski, E., Fox, C.P., Schorb, E., Celico, C.,... Illerhaus, G. (2022). 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. Leukemia. https://doi.org/10.1038/s41375-022-01582-5

MLA:

Ferreri, Andres J. M., et al. "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." Leukemia (2022).

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