Andrés J M Ferreri1, Giovanni Donadoni2, Maria Giuseppina Cabras2, Caterina Patti2, Michael Mian2, Renato Zambello2, Corrado Tarella2, Massimo Di Nicola2, Alfonso M D'Arco2, Gianluca Doa2, Marta Bruno-Ventre2, Andrea Assanelli2, Marco Foppoli2, Giovanni Citterio2, Alessandro Fanni2, Antonino Mulè2, Federico Caligaris-Cappio2, Fabio Ciceri2. 1. Andrés J.M. Ferreri, Giovanni Donadoni, Marta Bruno-Ventre, Andrea Assanelli, Marco Foppoli, Giovanni Citterio, Federico Caligaris-Cappio, and Fabio Ciceri, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute; Massimo Di Nicola, Istituto Nazionale dei Tumori, Milano; Maria Giuseppina Cabras and Alessandro Fanni, Hospital Businco, Cagliari; Caterina Patti and Antonino Mulè, Hospital "V. Cervello," Palermo; Michael Mian, Ospedale di Bolzano, Bolzano; Renato Zambello, Azienda Ospedaliera di Padua, University of Padua, Padua; Corrado Tarella, Azienda Ospedaliera Ordine Mauriziano-Umberto I, University of Turín, Turín; Alfonso M. D'Arco, Polo Oncologico Nocera-Pagani, Nocera Inferiore; and Gianluca Doa, Azienda Ospedaliera di Nuoro, Nuoro, Italy. ferreri.andres@hsr.it. 2. Andrés J.M. Ferreri, Giovanni Donadoni, Marta Bruno-Ventre, Andrea Assanelli, Marco Foppoli, Giovanni Citterio, Federico Caligaris-Cappio, and Fabio Ciceri, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute; Massimo Di Nicola, Istituto Nazionale dei Tumori, Milano; Maria Giuseppina Cabras and Alessandro Fanni, Hospital Businco, Cagliari; Caterina Patti and Antonino Mulè, Hospital "V. Cervello," Palermo; Michael Mian, Ospedale di Bolzano, Bolzano; Renato Zambello, Azienda Ospedaliera di Padua, University of Padua, Padua; Corrado Tarella, Azienda Ospedaliera Ordine Mauriziano-Umberto I, University of Turín, Turín; Alfonso M. D'Arco, Polo Oncologico Nocera-Pagani, Nocera Inferiore; and Gianluca Doa, Azienda Ospedaliera di Nuoro, Nuoro, Italy.
Abstract
PURPOSE: Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial 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 intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual 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 × 10(6)/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.
PURPOSE: Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial 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 intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual 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 × 10(6)/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.
Authors: Agnieszka Korfel; Marc Chamberlain; Ed Neuwelt; Eckhard Thiel; Nancy Doolittle; Uwe Schlegel; Martin Dreyling; James Rubenstein; Lars Fischer; Magnus Björkholm; Peter Martus; Michael Weller; Michael Glantz Journal: J Clin Oncol Date: 2016-03-21 Impact factor: 44.544
Authors: Francisco-Javier Peñalver; Juan-Manuel Sancho; Adolfo de la Fuente; María-Teresa Olave; Alejandro Martín; Carlos Panizo; Elena Pérez; Antonio Salar; Alberto Orfao Journal: Haematologica Date: 2016-10-20 Impact factor: 9.941
Authors: Dai Chihara; Nathan H Fowler; Yasuhiro Oki; Michelle A Fanale; Luis E Fayad; Jason R Westin; Fredrick B Hagemeister Journal: Br J Haematol Date: 2016-08-09 Impact factor: 6.998
Authors: Tarec Christoffer El-Galaly; Chan Yoon Cheah; Mette Dahl Bendtsen; Grzegorz S Nowakowski; Roopesh Kansara; Kerry J Savage; Joseph M Connors; Laurie H Sehn; Neta Goldschmidt; Adir Shaulov; Umar Farooq; Brian K Link; Andrés J M Ferreri; Teresa Calimeri; Caterina Cecchetti; Eldad J Dann; Carrie A Thompson; Tsofia Inbar; Matthew J Maurer; Inger Lise Gade; Maja Bech Juul; Jakob W Hansen; Staffan Holmberg; Thomas S Larsen; Sabrina Cordua; N George Mikhaeel; Martin Hutchings; John F Seymour; Michael Roost Clausen; Daniel Smith; Stephen Opat; Michael Gilbertson; Gita Thanarajasingam; Diego Villa Journal: Eur J Cancer Date: 2018-02-21 Impact factor: 9.162