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

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, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., Celico, C., …IELSG32 study investigators. (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, 36(7), 1870-1878. https://doi.org/10.1038/s41375-022-01582-5

• 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