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11569 Background: Sarcomas are rare mesenchymal neoplasms with substantial histologic and tumor microenvironment heterogeneity, leading to varied treatment responses, particularly to immunotherapy. Because of the heterogeneity of response rates and high risk of disease progression, further determinations of which patients are most likely to benefit from immunotherapy are crucial. In this study, we aim to characterize factors associated with response to immune checkpoint inhibitors (ICIs). Methods: 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care were analyzed. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtype, ICI regimen, tumor mutational burden (TMB), and PD-L1. Results: The most common histologic subtypes analyzed were leiomyosarcoma (LMS, n=48), liposarcoma (LPS, n=27), and undifferentiated pleomorphic sarcoma (UPS, n=18). Immunotherapy regimens primarily consisted of ipilimumab and nivolumab (77.8%), pembrolizumab (14.8%), and nivolumab monotherapy (6.0%). Median OS for all patients was 12.8 months. Response rates across all sarcomas were complete response (CR) 3.2%, partial response (PR) 13.4%, stable disease (SD) 30%, and progression of disease (PD) 53.2%. The ORR was higher in patients treated with pembrolizumab (21.9%) than with ipilimumab and nivolumab (14.3%). The histologic subtypes with the highest ORR were Kaposi sarcoma (KS, 66.7%), alveolar soft part sarcoma (ASPS, 50%), angiosarcoma (AS, 33.3%), myxofibrosarcoma (MFS, 28.6%), and UPS (27.8%). The subtypes with the lowest ORR were osteosarcoma (OS, 0%), synovial sarcoma (SS, 0%), and LPS (3.7%). The subtypes with the highest median PFS were KS (median not reached, NR), ASPS (NR), MFS (27.3 mo), and UPS (11.3 mo). Overall TMB (n=118) was low with a median of 2 mut/MB. Only 4 patients (3.3%) had a TMB ≥10, with a corresponding ORR of 25%. Overall PD-L1 expression (n=93 with TPS or CPS) was also low with a median of 0%. However, positive PD-L1 (n=36/93, > 1%) was associated with better ORR (27.8%, 10/36). 16.2% of patients discontinued immunotherapy due to autoimmune adverse effects; the most common were pneumonitis (18.4%), colitis (15.8%), arthritis (13.2%), and hepatitis (13.2%). Conclusions: Response and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the best ORR and longest PFS while OS, SS, and LPS were the lowest. TMB ≥10 and PD-L1 expression also correlated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs. Table: see text
Lee et al. (Sat,) studied this question.