Temozolomide in Relapse/Refractory Primary Vitreo-Retinal Lymphoma (R/R PVRL): A New Effective, Well-Tolerated and Cheap Reference. Result of a Study on Behalf of the LOC Network
2017
Abstract Background: PVRL is a very rare subset of non Hodgkin lymphoma, usually arising in elderly patients and characterized by a high level of relapse, with more than 60% of cases relapsingin brain, and a short overall survival (OS). There is no consensus on treatment (Tt)procedures, and prospective comparative studies do not exist. Options are systemic chemotherapy (SC),radiotherapy or intraocular injection of methotrexate (IM). Publication on R/R PVRL are exceptional, autologous stem cell transplantation (ASCT) is effective but in patient in complet response (CR). New drugs as lenalidomide (Len) and ibrutinib (Ib) have been published as effective in few cases but have a limited progression free survival (PFS), need a prolonged treatment and are very expensive. Temozolomide (TMZ) is a second generation, orally administered, DNA alkylating agent with excellent bioavailability in the CNS and is well tolerated. Methods: Inclusion criteria were a diagnosis established on cytological, phenotypical, biological (IL10 and IL6) and molecular analysis after vitrectomy.Tt consisted in TMZ 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 in the aqueous humor. Four centers of the French LOC network participated to this retrospective study. Results: 19 patients were analyzed, 6 males and 13 females, mean age 75 years [35-90]. One patient had PCNSL associated with PVRL. TMZ was 2nd line Tt for 8 patients, 3rd line for 6, 4th for 2, 5th for 1. Two patients, aged 85 and 90 years old, were in 1st line. Prior to TMZ, 12 patients received SC with at high dose methotrexate containing regimen, 3 received high dose cytarabin and 2 were only treated with IM. Two patients previously received an ASCT conditioned by thiotepa, cyclophosphamide and busulfan, one relapsed after Len and one after Ib. Median duration of TMZ treatment was 5,1 months (range 1 to 40). Median follow-up is 25 months (range 12 to 102). The objective overall response rate (ORR) is 78%. Thirteen patients obtained a CR (67%), with one patient with both ocular and cerebral CR, 2 patients obtained a PR (11%) and 4 had a progressive disease (PD). All but one had stopped TMZ and CR was persistent with a median duration of response after stopping TMZ of 37 months (range 25 to 49). One patient who had undergone ASCT before TMZ is still in CR 102 months after start of treatment and 61 months after stopping TMZ. Median OS is not reached and PFS is 14 months. No grade 3/4 toxicity has been described. Conclusion: This study represents the biggest series ever described with an homogeneous treatment in R/R PVRL. TMZ appears as a safe, effective and cheap Tt of R/R PVRL, even after high dose chemotherapy, ASCT, Len and Ib. Disclosures Leblond: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Soubeyran: Pierre Fabre: Honoraria; SPECTRUM: Honoraria; TEVA: Honoraria; Roche: Research Funding; CELGENE: Honoraria.
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