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 |
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Authors: | Giada Licata Maurizio Frezzato Niccolò Frungillo Fiorella Ilariucci Caterina Stelitano Antonella Ferrari Mariella Sorarù Fabrizio Vianello Luca Baldini Ilaria Proserpio Marco Foppoli Andrea Assanelli Michele Reni Federico Caligaris‐Cappio Andrés J M Ferreri |
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Institution: | 1. Unit of Lymphoid Malignancies, Division of Onco‐Hematological Medicine, Department of Onco‐Hematology, San Raffaele Scientific Institute, , Milan, Italy;2. Hematology Unit, S. Bortolo Hospital, , Vicenza, Italy;3. Medical Oncology Unit, S. Paolo Hospital, , Milan, Italy;4. Hematology Unit, S. Maria Nuova Hospital, , Reggio Emilia, Italy;5. Hematology Unit, Melacrino Morelli Hospital, , Reggio Calabria, Italy;6. Sant'Andrea Hospital, Facoltà di Medicina e Psicologia, University ‘Sapienza’ Rome, , Rome, Italy;7. Medical Oncology Unit, Hospital of Camposampiero, , Padova, Italy;8. Hematology and Immunology Unit, Universitary Hospital of Padova, , Padova, Italy;9. Division of Hematology, Fondazione IRCCS Cà Granda OM Policlinico, , Milan, Italy;10. Medical Oncology Unit, Ospedale di Circolo, , Varese, Italy;11. Hematology and TMO Unit, Department of Onco‐Hematology, San Raffaele Scientific Institute, , Milan, Italy |
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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/m2, day 0; ifosfamide 2 g/m2/day, days1–3; etoposide 250 mg/m2, 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. Copyright © 2012 John Wiley & Sons, Ltd. |
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Keywords: | primary CNS lymphoma rituximab ifosfamide etoposide autologous stem cell transplantation |
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