P007 | HIGH-DOSE METHOTREXATE-CYTARABINE-BASED CHEMOTHERAPY COMBINED WITH INTRAOCULAR DRUG INJECTIONS FOR PRIMARY VITREORETINAL LYMPHOMA: EXPERIENCE FROM TWO ITALIAN REFERRAL CENTRES

Primary vitreoretinal lymphoma (PVRL), a rare subtype of large B-cell lymphoma affecting solely the vitreous and/or retina, often disseminates to the brain. Optimal treatment remains unclear: local therapies (intravitreal drug injections and ocular radiation (ORT)) show limited CNS protection, while benefit of intensified treatments, such as those used in PCNSL, is under investigation. This study evaluates the efficacy and tolerability of HDMTX-cytarabine(araC)-based chemo plus IV drug injections in PVRL patients (pts) treated at 2 Italian centers. Twenty-six consecutive pts with PVRL treated with HDMTX-araC-based chemo ± intravitreal injections (median age 62, range 39-74, 14 M) between 2015 and 2024 were reviewed. Median time from symptom onset to diagnosis was 13 months (range 1-36). Suggestive ophthalmologic findings led to vitrectomy in all pts, which was bilateral in 4 (15%): PVRL suspicion was confirmed by cytology in 4 pts (15%), molecular markers (MYD88, IL-10, IgH) in ocular fluids in 3 (12%), and both in 19 (73%). MATRix regimen was the most used systemic chemo (16/26 (62%) pts); 20 pts (77%) received intravitreal MTX injections (median 25, range 14-25), while the other 6 (23%) received consolidation (ASCT=2, ORT=4). Intravitreal chemo was well tolerated without cases of grade ≥3 toxicity, or discontinuations due to adverse events. The best response was CR in 23/25 (92%) evaluable pts and PR in 1 (4%), resulting in an ORR of 96% (95%CI= 88-100); 1 pt was not evaluable because treated at another center. At a median follow-up of 27 months (range 7-113), 14/25 (56%) pts experienced relapse: 5 (36%) into the eyes, 5 (36%) into the brain, and 4 (28%) concomitantly in both sites. Overall, 11 pts relapsed in the brain with a median brain-free survival of 62 months, while median ocular-free survival was not reached. Median PFS was 18 months. Seven pts (27%) died (lymphoma=5, sepsis=1, unk=1). Notably, 5 of the 7 pts treated with bilateral vitrectomy and/or consolidation are still relapse free, the other 2 relapsed into the eyes; none of them died at 8-44 months. The combination of HDMTX-araC-based chemotherapy and intravitreal drug injections shows a high response rate with no unexpected toxicity in PVRL. However, half of the pts experience recurrence, with relapses evenly distributed among the eyes, brain, and both sites. The potential benefits of bilateral vitrectomy, consolidative ASCT, and ORT appear promising and warrant further investigation.