Abstract 374P
Background
The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma (PCNSL), currently relies on the histopathology of vitreous biopsy. Misdiagnoses occasionally happen due to the extremely low number of cancerous cells in vitreous fluid, and the examination of visual acuity and fundus can be subjective and inaccurate during VRL treatment monitoring.
Methods
This study enrolled 16 VRL patients whose baseline aqueous humor (AH) and/or vitreoretinal fluid (VF) specimen subject to comprehensive genomic profiling using targeted next generation sequencing. Serial post-treatment AH or VF samples were also available for five patients. Cerebrospinal fluid (CSF) sampling and MRI examination were performed for patients showing symptoms of CNS metastasis.
Results
Mutational profiles of baseline samples revealed that MYD88 (L265P) and/or CD79B activating mutations were present in 62.5% (10/16) of the cohort, whereas about 56% (9/16) of the patients carried IRF4 mutations and half (8/16) had CDKN2B copy-number loss, both of which the frequency was much higher in VRL than PCNSL. Mutations identified in baseline AH or VF specimens were highly concordant with comparable allele frequencies (AFs). Moreover, partial response was observed in 1 out of 7 patients (objective response rate [ORR], 14%) treated with ibrutinib, a BTK inhibitor that has demonstrated anti-tumor efficacy in PCNSL (ORR: 65%). Changes of variant AFs observed in post-ibrutinib samples were closely associated with changes in interleukin 10 (IL-10) levels indicative of treatment response. In addition, both AH and VF biopsies appeared to have more mutations detected at higher AFs when compared to CSF samples in patients who had signs of CNS metastasis (N = 5).
Conclusions
AH represents a substitute for vitreous fluid as a rich source of eye-specific tumoral genomic information, and we demonstrated that molecular profiling of the AH has clinical utility for VRL diagnosis and treatment monitoring. While different genomic traits may underlie variability in response to ibrutinib between VRL and PCNSL, further research of larger sample size is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sun Yat-sen Univerisity Cancer Center.
Funding
The National Science & Technology Major Project.
Disclosure
X. Wang: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. Y. Ma: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. Q. Ou: Financial Interests, Personal, Full or part-time Employment: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.