High Efficiency of ICE (Ifosfamide-Carboplatin-Etoposide) in Relapse/Refractory Primary Central-Nervous System and Intra-Ocular Non Hodgkin Lymphoma, After First Line Treatment Containing High Doses of Methotrexate and Cytarabine. A Monocentric Retrospective Study From 2010 to 2012 On 17 Cases

Primary central nervous system lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL) are at very high risk of relapse after a first line treatment, and then carry a very poor prognosis. Autologous stem cell transplantation (ASCT) can offer prolonged responses but its results clearly depend on efficiency of salvage chemotherapy (Soussain, haemtologica, 2012). Since recent publications on first line treatment of PCNSL and PIOL recommend high dose methotrexate (Mtx) and cytarabine (AraC) (Ferreri, Lancet 2009), salvage chemotherapy must use other drugs with high level of penetration in the central nervous system (CNS). In this setting, ICE regimen, validated in systemic non Hodgkin lymphoma, seems to be appropriated but no data is published in PCNSL and PIOL.

From june 2010 to may 2012, all relapse/refractory PCNSL and PIOL treated in first line by high doses of Mtx and AraC in the Pitie-Salpetriere Hospital, Paris, France, where treated by ICE regimen : ifosfamide (5g/m² at day 2), carboplatine (AUC 5 at day 2) and etoposide (100mg/m²/d days 1 to 3). Doses where adapted on patient general status and ASCT proposed when possible.

Seventeen patients have been treated, 7 females and 10 males, median age 62 [28–84]. Four where refractory and 13 in relapse, with a mean progression free survival (PFS) of 368 days [85–1763], 4 had a second line, one a third before ICE. At moment of ICE treatment, localizations where 10 CNS, 2 CNS + PIOL, 3 PIOL and 2 meningitis. The mean number of cycles was 4 [1–6] and 4 patients needed a dose reduction. During treatment, grade 3/4 WHO toxicities where: 6 neutropenic fever (one death), 5 anemia, 9 neutropenia, 10 thrombopenia and one CNS complication (coma and hypersalivation). ASCT have been made in 6 patients (5 in CR, 1 in PR) and are pending in 3. Complete response (CR) have been obtained in 13 patients (76%), partial in 2. With a mean follow-up of 405 days, 6/15 patients in response relapsed (only one after ASCT), in a median of 81 days, 9 patients died (7 by progression, one during treatment and one in CR). Median Overall survival (OS) was 220 days for all patients but was not reached in case of ASCT.

ICE regimen is very effective in relapse/refractory PCNSL and PIOL heavily treated by high dose Mtx and AraC. This efficacy can allow to perform ASCT in eligible patients, chemosensitivity being the most important factor influencing the OS and PFS after ASCT. ICE can represent a new standard in this setting.

Leblond:Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.