title: 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.
abstract: 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 ≤75 years old with failed PCNSL treated with R-IE regimen (rituximab 375 mg/m(2) , day 0; ifosfamide 2 g/m(2) /day, days1-3; etoposide 250 mg/m(2) , day 1; four courses). Twenty-two patients (median age 60 years; 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 24 months, 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.
authors.affiliation: Unit of Lymphoid Malignancies, Division of Onco-Hematological Medicine, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mappa
authors.forename: Emerenziana
authors.initials: E
authors.lastname: Marturano
authors.forename: Giada
authors.initials: G
authors.lastname: Licata
authors.forename: Maurizio
authors.initials: M
authors.lastname: Frezzato
authors.forename: Niccolò
authors.initials: N
authors.lastname: Frungillo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferrari
authors.forename: Mariella
authors.initials: M
authors.lastname: Sorarù
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vianello
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Proserpio
authors.forename: Marco
authors.initials: M
authors.lastname: Foppoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003390:Cranial Nerve Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005134:Eye Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D016879:Salvage Therapy; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D005047:Etoposide; D007069:Ifosfamide; D008727:Methotrexate