Combined intravitreal methotrexate and immunochemotherapy followed by reduced‐dose whole‐brain radiotherapy for newly diagnosed B‐cell primary intraocular lymphoma

Abstract

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.

CD79B mutations in primary vitreoretinal lymphoma: Diagnostic and prognostic potential

“…The two‐year CNS lymphoma‐free survival (CLFS) was 58.3%, whereas that of 8 patients treated with intravitreal MTX alone was 37.5%. Kaburaki et al combined intravitreal MTX injections, MTX‐based systemic induction chemotherapy, consolidation high‐dose cytarabine, and reduced‐dose whole‐brain radiation therapy (23 Gy) for the treatment of PVRL. Their study showed reduced CNS relapse (4‐year progression‐free survival: 72.7%; overall survival: 88.9%).…”

“…Their study showed reduced CNS relapse (4‐year progression‐free survival: 72.7%; overall survival: 88.9%). However, approximately 30% of patients still experienced CNS relapse . There is a strong necessity to establish a predictive marker for CNS disease development and risk stratification‐based treatment strategies for preventing the development of CNS disease.…”

Clinical features and outcomes of secondary intraocular lymphoma

“…Several studies reported that combination therapy combined with intraocular and systemic chemotherapy and radiotherapy of PIOL has improved clinical outcomes; with 4‐year OS rates of 75–86·3% (Lee et al , ; Kaburaki et al , ). However, SIOL have only been reported in several case reports with few integrated results.…”

Intraocular chemotherapy for vitreoretinal lymphoma: A review

“…A smaller 2018 report from Charles University and General Hospital University (Prague, Czech Republic) provided additional data in support of a combined extensive and local treatment approach to VRL: in 10 patients with primary VRL, combined therapy with intravitreal methotrexate extended progression‐free survival, but not overall survival. Two non‐comparative studies from Japan involving 27 patients with VRL provide further support for combination treatment, including intravitreal methotrexate as ocular therapy, for primary VRL . While the best approach to managing VRL continues to be discussed, choice of treatment also will depend on general physical health and medical history, as noted in the 2015 European Association for Neuro‐Oncology Guidelines …”

“…Subsequent to the original clinical case series, medical centres in North America, Europe, the Middle East and Asia also have reported their experience in treating groups totalling at least 177 eyes of 114 patients with VRL, [34][35][36][37][38][39][40] as well as multiple individual patients, [41][42][43][44][45] using intravitreal methotrexate injections. Additional reports have described groups of patients suffering from VRL, who received a range of treatments that included methotrexate and/or rituximab intravitreal injections (see below).…”