1503P Prevalence and clinical characteristics of metastatic synovial sarcoma (mSS) patients with tumours expressing NY-ESO-1 antigen (NY+) and who are HLA-A*02:01, *02:05 or *02:06 allele positive (HLA+): Cohort study from the French sarcoma group

Abstract

Letetresgene autoleucel is a genetically engineered NY-ESO-1–specific TCR T-cell therapy being investigated in mSS patients whose tumours express the NY-ESO-1 antigen and who are HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 allele positive (NY+/HLA+). Our objective was to understand the prevalence & clinical characteristics of NY+/HLA+ mSS patients in a nationally representative population. This was a retrospective cohort study in French national reference centres. Adult patients with histologically confirmed diagnosis of mSS ≥1 Jan 2000 and registered in the French sarcoma database (NETSARC+) with available FFPE archival primary tumour samples & clinical data were included. Tumour samples were examined for NY-ESO-1 expression (by IHC, NY+ defined as ≥30% tumour cells staining with 2+/3+ stain intensity) & HLA sub-type (by RNA-seq using Optitype genotyping algorithm). 109 mSS patients met study criteria; with NY-ESO-1 expression available for 106, HLA status for 94, and both statuses for 91 patients. 61% of patients were NY+ with similar NY+ prevalence among HLA+ and HLA- populations (56% and 62%, resp) and by line of systemic treatment (in 1L: 60%, 2L: 59%). Mean age of tumour samples was 11.0 years (NY+ 10.4 yrs, NY- 12.0 yrs, p=0.151). 45% of patients were HLA+ with similar HLA+ prevalence among NY+ and NY- populations (43% and 49%, resp) and by line (in 1L: 44%, 2L: 45%). Overall, 25% (23/91) were dual positive (NY+/HLA+, in 1L: 23%, 2L: 22%). Characteristics of NY+/HLA+ vs. NY- and/or HLA- patients reported in table.Table: 1503PPatient and tumour characteristicsAll (n=109), includes 17 patients with missing NY/HLA dataNY+/HLA+ (n=23) in primary tumour samplesNY- and/or HLA- (n=69) in primary tumour samplesFisher exact test (p>0.05 = NS)Male55%61%58%NSPrimary tumour location = limbs60%87%49%p=0.003Primary tumour size ≥90 mm57%70%56%NSDiagnosed with metastatic disease ≤55 yrs age71%78%68%NSSite of first metastasis = lung only70%91%67%p=0.029Only one metastatic site87%96%86%NSDiagnosed with metastatic disease ≤ year 201045%65%41%NSTime from localised to metastatic diagnosis ≤12 months29%41%29%NS Open table in a new tab Nationally representative prevalence and clinical profile of mSS patients with NY+/HLA+ tumours were previously unknown and have been documented by this study. Among primary tumour samples, no relationship was observed between NY-ESO expression and age of samples, HLA sub-type, or line of treatment.