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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

Item Type:Article
Title: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
Creators Name:Ferreri, A.J.M. and Cwynarski, K. and Pulczynski, E. and Fox, C.P. and Schorb, E. and Celico, C. and Falautano, M. and Nonis, A. and La Rosée, P. and Binder, M. and Fabbri, A. and Ilariucci, F. and Krampera, M. and Roth, Al. and Hemmaway, C. and Johnson, P.W. and Linton, K.M. and Pukrop, T. and Gørløv, J.S. and Balzarotti, M. and Hess, G. and Keller, U. and Stilgenbauer, S. and Panse, J. and Tucci, A. and Orsucci, L. and Pisani, F. and Zanni, M. and Krause, S.W. and Schmoll, H.J. and Hertenstein, B. and Rummel, M. and Smith, J. and Thurner, L. and Cabras, G. and Pennese, E. and Ponzoni, M. and Deckert, M. and Politi, L.S. and Finke, J. and Ferranti, A. and Cozens, K. and Burger, E. and Ielmini, N. and Cavalli, F. and Zucca, E. and Illerhaus, G.
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.
Keywords:Antineoplastic Combined Chemotherapy Protocols, Autologous Transplantation, Central Nervous System Neoplasms, Combined Modality Therapy, Cytarabine, Hematopoietic Stem Cell Transplantation, Lymphoma, Methotrexate, Quality of Life, Rituximab, Thiotepa
Publisher:Nature Publishing Group
Page Range:1870-1878
Date:July 2022
Official Publication:https://doi.org/10.1038/s41375-022-01582-5
PubMed:View item in PubMed

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