Defining Vitreoretinal Lymphoma
Treatment of R/R PVRL
At relapse, a combination of systemic therapy with MTX intraocular injection or ocular radiotherapy, similar to the primary treatment, will rapidly improve vision. At relapse, chemotherapy followed by Autologous stem cell transplantation (ASCT) is also considered for patients at an age capable of ASCT. Chemotherapy + ASCT which focuses on the IC regimen of Thiotepa, Busulfan, and Cyclophosphamide, is being evaluated in its ability to avoid the Blood Retinal Barrier (BRB) in PVRL patients. A pilot study reported promising results for refractory PVRL patients after inducting chemotherapy based on HD MTX and HD cytarabine as part of treatment. Five patients who received IC + ASCT treatment achieved CR, with no CNS relapse after ASCT. The median value of the follow-up period was 17 months. These studies confirmed that the remedy displayed high efficacy/outcomes for both R/R PCNSL patients and PVRL with no significant difference between the two. Although these statements are based on a small-scale study of PVRL patients, the rarity of this disease and lack of comparative studies means that IC + ASCT can still be considered for young patients with PVRL relapse and no serious complications. In Japan, a regimen of ASCT with pre-treatment of BuTT (Busulfan and Thiotepal) is approved by insurance.
Single-agent and targeted therapy
In a retrospective study of 21 patients (relapse, n = 19, first line, n = 2), single-agent temozolomide displayed encouraging results with a favorable toxicity profile. The Median follow-up period was 42 months, the median PFS value was 12 months, and the number of CNS relapses was 5.
2) Lenalidomide (as a single agent or in combination with rituximab) and ibrutinib
Two targeted therapies, Lenalidomide (as a single agent or in combination with rituximab) and ibrutinib, underwent phase I and prospective proof-of-concept Phase II trials. These therapies are known to have high efficacy against systemic DLBCL and a preferential anti-lymphoma activity against the ABC DLBCL subtype. In the REVRI study, rituximab was administered intravenously at 375/m2 on day 1, and lenalidomide was administered at 20mg/day for the first cycle. The administration of lenalidomide was then changed to 25 mg/day on days 1-21 thereafter for eight 28 day cycles. In the study, 50 patients – 17 of whom had intraocular lesions (11 patients with R/R PVRL and 6 patients with brain and eye lesions) – were enrolled. The CR rate was 35%, and the PFS median value of PVRL patients was 9.2 months in the patient subgroup. The Median OS value for PVRL patients was not reached and was significantly longer than that for PCNSL patients (P=0.03).
3) Single-agent Ibrutinib
The prospective, multicenter, phase II LOC study evaluated the performance of ibrutinib as a single agent in patients with R/R PCNSL and PVRL. The study also included 14 patients with R/R PVRL. The study reported that 86% of the patients with intraocular lesions achieved an overall response rate after 2 months, of which 50% had a CR. The PFS median value of PVRL patients was 23 months. One case of CNS relapse was reported after the median follow-up period of 26 months.