TY - JOUR
T1 - Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R-IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high-dose methotrexate-based chemotherapy
AU - Mappa, Silvia
AU - Marturano, Emerenziana
AU - Licata, Giada
AU - Frezzato, Maurizio
AU - Frungillo, Niccolò
AU - Ilariucci, Fiorella
AU - Stelitano, Caterina
AU - Ferrari, Antonella
AU - Sorarù, Mariella
AU - Vianello, Fabrizio
AU - Baldini, Luca
AU - Proserpio, Ilaria
AU - Foppoli, Marco
AU - Assanelli, Andrea
AU - Reni, Michele
AU - Caligaris-Cappio, Federico
AU - Ferreri, Andrés J M
PY - 2013/9
Y1 - 2013/9
N2 - Despite a high proportion of patients with primary CNS lymphoma (PCNSL) experiences failure after/during first-line treatment, a few studies focused on salvage therapy are available, often with disappointing results. Herein, we report feasibility and activity of a combination of rituximab, ifosfamide and etoposide (R-IE regimen) in a multicentre series of patients with PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. We considered consecutive HIV-negative patients ≤75years old with failed PCNSL treated with R-IE regimen (rituximab 375mg/m2, day 0; ifosfamide 2g/m2/day, days1-3; etoposide 250mg/m2, day1; four courses). Twenty-two patients (median age 60years; range 39-72; male/female ratio: 1:4) received R-IE as second-line (n=18) or third-line (n=4) treatment. Eleven patients had refractory PCNSL, and 11 had relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of the 88 planned courses were actually delivered; only one patient interrupted R-IE because of toxicity. Grade 4 hematological toxicity was manageable; a single case of grade 4 non-hematological toxicity (transient hepatotoxicity) was recorded. Response was complete in six patients and partial in three (overall response rate=41%; 95%CI: 21-61%). Seven patients were successfully referred to autologous peripheral blood stem cell collection; four responders were consolidated with high-dose chemotherapy supported by autologous stem cell transplant. At a median follow-up of 24months, eight responders did not experience relapse, two of them died of neurological impairment while in remission. Six patients are alive, with a 2-year survival after relapse of 25±9%. We concluded that R-IE is a feasible and active combination for patients with relapsed/refractory PCNSL. This regimen allows stem cell collection and successful consolidation with high-dose chemotherapy and autologous transplant.
AB - Despite a high proportion of patients with primary CNS lymphoma (PCNSL) experiences failure after/during first-line treatment, a few studies focused on salvage therapy are available, often with disappointing results. Herein, we report feasibility and activity of a combination of rituximab, ifosfamide and etoposide (R-IE regimen) in a multicentre series of patients with PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. We considered consecutive HIV-negative patients ≤75years old with failed PCNSL treated with R-IE regimen (rituximab 375mg/m2, day 0; ifosfamide 2g/m2/day, days1-3; etoposide 250mg/m2, day1; four courses). Twenty-two patients (median age 60years; range 39-72; male/female ratio: 1:4) received R-IE as second-line (n=18) or third-line (n=4) treatment. Eleven patients had refractory PCNSL, and 11 had relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of the 88 planned courses were actually delivered; only one patient interrupted R-IE because of toxicity. Grade 4 hematological toxicity was manageable; a single case of grade 4 non-hematological toxicity (transient hepatotoxicity) was recorded. Response was complete in six patients and partial in three (overall response rate=41%; 95%CI: 21-61%). Seven patients were successfully referred to autologous peripheral blood stem cell collection; four responders were consolidated with high-dose chemotherapy supported by autologous stem cell transplant. At a median follow-up of 24months, eight responders did not experience relapse, two of them died of neurological impairment while in remission. Six patients are alive, with a 2-year survival after relapse of 25±9%. We concluded that R-IE is a feasible and active combination for patients with relapsed/refractory PCNSL. This regimen allows stem cell collection and successful consolidation with high-dose chemotherapy and autologous transplant.
KW - Autologous stem cell transplantation
KW - Etoposide
KW - Ifosfamide
KW - Primary CNS lymphoma
KW - Rituximab
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UR - http://www.scopus.com/inward/citedby.url?scp=84887018790&partnerID=8YFLogxK
U2 - 10.1002/hon.2037
DO - 10.1002/hon.2037
M3 - Article
C2 - 23161567
AN - SCOPUS:84887018790
VL - 31
SP - 143
EP - 150
JO - Hematological Oncology
JF - Hematological Oncology
SN - 0278-0232
IS - 3
ER -