High doses of antimetabolites followed by high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation in patients with systemic B-cell lymphoma and secondary CNS involvement: Final results of a multicenter phase II trial

Andrés J M Ferreri, Giovanni Donadoni, Maria Giuseppina Cabras, Caterina Patti, Michael Mian, Renato Zambello, Corrado Tarella, Massimo Di Nicola, Alfonso M. D'Arco, Gianluca Doa, Marta Bruno-Ventre, Andrea Assanelli, Marco Foppoli, Giovanni Citterio, Alessandro Fanni, Antonino Mulè, Federico Caligaris-Cappio, Fabio Ciceri

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Abstract

Purpose Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an mportant, unmet clinical need. Herein, we report the final results of a multicenter phase II tria addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma Patients and Methods HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≥ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intratheca iposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrua was 38 patients Results Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 106/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ±11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. Conclusion The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.

Original languageEnglish
Pages (from-to)3903-3910
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number33
DOIs
Publication statusPublished - Nov 20 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ferreri, A. J. M., Donadoni, G., Cabras, M. G., Patti, C., Mian, M., Zambello, R., Tarella, C., Di Nicola, M., D'Arco, A. M., Doa, G., Bruno-Ventre, M., Assanelli, A., Foppoli, M., Citterio, G., Fanni, A., Mulè, A., Caligaris-Cappio, F., & Ciceri, F. (2015). High doses of antimetabolites followed by high-dose sequential chemoimmunotherapy and autologous stem-cell transplantation in patients with systemic B-cell lymphoma and secondary CNS involvement: Final results of a multicenter phase II trial. Journal of Clinical Oncology, 33(33), 3903-3910. https://doi.org/10.1200/JCO.2015.61.1236