Immune checkpoint blockade (ICB) in advanced/metastatic leiomyosarcoma (LMS): Real-world cohort from MD Anderson.

Abstract

e23545 Background: LMS is an aggressive soft-tissue sarcoma with an immunologically “cold” tumor microenvironment and historically poor responsiveness to ICB. With limited benefit from cytotoxic therapy beyond first-line and low ICB monotherapy activity, defining real-world ICB outcomes and identifying patients (pts) who may benefit remain an unmet clinical need. Methods: Adults with advanced/metastatic LMS treated with ICB at MD Anderson (2010–2025) were retrospectively identified via the pharmacy database. Response was assessed per trial RECIST v1.1 when available; otherwise, partial response/stable disease/progressive disease (PR/SD/PD) were extracted from documentation with radiology impressions. Disease control rate (DCR) was defined as PR+SD, and clinical benefit rate (CBR) as PR or SD ≥6 months (mo). Toxicity was graded per CTCAE v5. Subgroups were compared using chi-square/Fisher’s exact tests. Progression-free survival (PFS) was estimated by Kaplan–Meier, compared by log-rank, and evaluated with Cox regression. Results: Among 41 pts (median age 59; 76% female), 90% (n = 37) had metastatic disease at ICB start, 59% (n = 24) had ≥2 prior systemic therapy lines; 90% (n = 37) had doxorubicin; 76% (n = 31) had gemcitabine. Metastases involved lung in 83% (n = 34), liver in 66% (n = 27), and bone in 32% (n = 13). Primary sites were uterus in 29% (n = 12), retroperitoneum in 39% (n = 16), and other soft-tissue sites in 32% (n = 13). Overall, 85% (35/41) received ICB on a trial and 90% (37/41) received combination therapy: 57% (21) dual ICB, 24% (9) investigational targeted combinations, 11% (4) with concomitant radiotherapy, and 8% (3) with TKI. Best response was PR in 2 pts (5%), SD in 24 (59%), and PD in 15 (37%), yielding DCR 63% and CBR 22%. CBR differed by LMS type: 0/12 uterine LMS (uLMS) vs 9/29 (31%) for soft-tissue LMS (ST-LMS; p = 0.04) and by primary site (retroperitoneum 19% [3/16] vs other sites 46% [6/13]; Fisher’s exact p = 0.008). Median PFS was 3 mo overall and was longer with DCR vs PD (4.5 vs 1.5 mo; p < 0.001). PFS was longer with lung metastases (4.1 vs 1.3 mo; p < 0.001) and shorter with bone metastases (2.7 vs 4.1 mo; p = 0.02) and with prior gemcitabine exposure (2.8 vs 4.5 mo; p = 0.03), reflecting heavier pretreatment. In multivariable Cox regression, lung metastases (aHR 0.06; p < 0.001), bone metastases (aHR 4.8; p < 0.001), prior gemcitabine exposure (aHR 2.4; p = 0.04), and trial participation (aHR 0.2; p = 0.002; reflecting selection/regimen differences) remained independently associated with PFS. Toxicity occurred in 51%, with grade ≥3 events in 24%. Conclusions: In this real-world cohort of ICB-treated advanced LMS, trial participation and lung metastases predicted better PFS while bone metastases and prior gemcitabine exposure predicted worse PFS. ST-LMS had greater CBR than uLMS. Translational efforts are ongoing to identify LMS-specific biomarkers of ICB response.