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: Silvia Mappa, Emerenziana Marturano, 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
• Journal: Hematological oncology (Hematol Oncol) Vol. 31 Issue 3 Pg. 143-50 (Sep 2013) ISSN: 1099-1069 [Electronic] England
• PMID: 23161567 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Rituximab
• Etoposide
• Ifosfamide
• Methotrexate

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Central Nervous System Neoplasms (drug therapy, radiotherapy, surgery)
• Combined Modality Therapy
• Cranial Irradiation
• Cranial Nerve Neoplasms (drug therapy, radiotherapy, surgery)
• Drug Administration Schedule
• Drug Evaluation
• Drug Resistance, Neoplasm
• Etoposide (administration & dosage, adverse effects)
• Eye Neoplasms (drug therapy, radiotherapy, surgery)
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Humans
• Ifosfamide (administration & dosage, adverse effects)
• Kaplan-Meier Estimate
• Lymphoma, Large B-Cell, Diffuse (drug therapy, radiotherapy, surgery)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Peripheral Blood Stem Cell Transplantation
• Recurrence
• Remission Induction
• Retrospective Studies
• Rituximab
• Salvage Therapy
• Survival Analysis
• Transplantation, Autologous
• Treatment Outcome