High Efficiency and Tolerance of Temozolomide in Relapse/Refractory Primary Intra-Ocular Lymphoma (R/R PIOL). a Retrospective Multicentric Study from the LOC Network

Background: PIOL, now named “primary vitreo-retinal lymphoma”, is a very rare subset of non Hodgkin lymphoma, usually arising in elderly patients and characterized by a high level of relapse, mainly in the first year, with more than 20% of cases relapsing in brain, and a short survival. There is no consensus on treatment procedures, even in first line, and prospective comparative studies do not exist. Classical attitudes are systemic chemotherapy (SC), often high dose methotrexate, radiotherapy or intraocular injection of methotrexate but publication on R/R PIOL are exceptional. New treatments are necessary, especially with a good tolerance profile. As Temozolomide (Te) hassome efficiency on primary-central-nervous-system lymphoma (PCNSL) we used this drug in R/R PIOL in our center.

Methods: Inclusion criteria were R/R PIOL and/or PIOL not eligible for IV chemotherapy. Diagnosis was established on cytological and molecular analysis after vitrectomy, and the absence of brain or meningeal localization verified by MRI and lumbar puncture. Treatment consisted in Te at 150mg/m² orally 5 days per month, without corticosteroid use, in absence of any response, dosage was increased to 200mg/m². A complete response was defined as a normalization of eye exam and intraocular interleukins 10 and 6 levels.

Results: Sixteen patients were analyzed, 3 males and 13 females, mean age 75 years [35-90]. All but two received systemic chemotherapy with at least high dose methotrexate and high dose cytarabin before Te, 8 were in second line, 4 in third, with 1 patient who relapsed after autologous stem-cell transplantation (ASCT) conditioned by thiotepa, cyclophosphamide and busulfan, and 2 in forth. The 2 patients treated in first line where more than 80 years old. Median duration of treatment was 5 months. The median follow-up (fu) is 16 months. Overall response rate is 75%, with 10 CR (63%) and 2 PR (13%). At the last fu, 7 patients are still in CR, with a median DFS of 13 months. The patient treated after ASCT relapse is still in CR at 62 months. The two old patients treated in first line are in CR at last fu. Two patients where treated a second time by Te after relapse, obtaining 2 new CR, one of 4 months, one persistent at 14 months. Median OS is not reached. Only 3 patients experienced hematological grade 3/4 toxicity.

Conclusion: This work represents the biggest study with an homogeneous treatment in R/R PIOL. Temozolomide appears as a safe and efficient treatment of R/R PIOL or in first line in patients in bad condition, even after high dose chemotherapy and/or in elderly patients. Longer follow-up, prospective and larger studies are necessary to confirm these data