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Diem Trang Nguyen, Nathalie Cassoux, Sylvain Choquet, Carole Soussain, Chloé Le Cossec, Antonio Omuro, Phuc Lehoang, Bahram Bodaghi, Khe Hoang Xuan, Valerie Touitou, Reseau LOC (INCa); Primary Oculo-Cerebral lymphoma (POCL): Efficacy of intravenous high-dose methotrexate (MTX) based polychemotherapy without radiotherapy on intraocular disease control. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6023. doi: https://doi.org/.
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Chemotherapy with radiotherapy (RT) is the current standard treatment of primary oculo-cerebral lymphoma (POCL) but exposes to a high risk of radiation-induced neurotoxicity, especially in the elderly. We recently reported encouraging results of 2 intravenous (IV) high-dose (HD) MTX based polychemotherapy regimens without RT in a randomized multicenter phase II trial (“CNS trial”) for primary central nervous system lymphoma patients over 60 years old (MPVA: HD-MTX, procarbazine, vincristine, and cytarabine versus HD-MTX-Tmz: MTX, temozolomide).The objective was to evaluate the efficacy of IV MTX-based chemotherapy on intraocular lymphoma (IOL) in POCL without RT.
Patients with pathologically proven POCL randomized in the CNS trial, with baseline and follow-up ocular evaluations available were retrospectively analysed. The primary study end-points were the ocular response and event-free survival. Secondary outcome measures were: cerebral event-free survival and overall survival (OS) of both treatments.
Thirteen patients out of 98 (9 males / 4 females, median age 63 years old) met the inclusion criteria. Six patients were randomized into the MPVA group and 7 into the MTX-Tmz group. Overall ocular complete response rate was 58% (MPVA: 67%, MTX-Tmz: 50% - p=0.99). Disease progressed in 17% of patients (MPVA: 17%, MTX-Tmz: 17%) and remained stable in 25% (MPVA: 17%, MTX-Tmz: 33%). With a median follow-up of 32 months, ocular relapse after an initial complete response was observed in 42% of patients (MPVA: 75%, MTX-Tmz: 67% - p=0.71). The median ocular event-free survival was 15 months (0-43) in the MPVA group, and 16.5 months (5-69) in the MTX-Tmz group (p=0.997). The median OS for the entire population was 32 months (6-69) without significant difference between the two groups (p=0.481), neither in the cerebral event-free survival (p=0.572). Systemic toxicities occurred in both groups (p>0.05) but were managable. Neurocognitve functions were well preserved.
IV HD MTX based polychemotherapy as first line treatment is active in IOL in the setting of POCL. MPVA and MTX-Tmz demonstrate similar efficacy. Despite a good response rate, relapses remain frequent and improvement of intra-ocular disease control is needed. Future chemotherapy regimens and treatment strategies have to focus on this issue.
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