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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

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    Authors
    Ferreri, A. J. M.
    Cwynarski, K.
    Pulczynski, E.
    Fox, C. P.
    Schorb, E.
    Celico, C.
    Falautano, M.
    Nonis, A.
    La Rosée, P.
    Binder, M.
    Fabbri, A.
    Ilariucci, F.
    Krampera, M.
    Roth, A.
    Hemmaway, C.
    Johnson, P. W.
    Linton, Kim M
    Pukrop, T.
    Gørløv, J. S.
    Balzarotti, M.
    Hess, G.
    Keller, U.
    Stilgenbauer, S.
    Panse, J.
    Tucci, A.
    Orsucci, L.
    Pisani, F.
    Zanni, M.
    Krause, S. W.
    Schmoll, H. J.
    Hertenstein, B.
    Rummel, M.
    Smith, J.
    Thurner, L.
    Cabras, G.
    Pennese, E.
    Ponzoni, M.
    Deckert, M.
    Politi, L. S.
    Finke, J.
    Ferranti, A.
    Cozens, K.
    Burger, E.
    Ielmini, N.
    Cavalli, F.
    Zucca, E.
    Illerhaus, G.
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    Affiliation
    Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy
    Issue Date
    2022
    
    Metadata
    Show full item record
    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.
    Citation
    Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, Celico C, 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. Springer Science and Business Media LLC; 2022.
    Journal
    Leukemia
    URI
    http://hdl.handle.net/10541/625305
    DOI
    10.1038/s41375-022-01582-5
    PubMed ID
    35562406
    Additional Links
    https://dx.doi.org/10.1038/s41375-022-01582-5
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41375-022-01582-5
    Scopus Count
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