Clinical activity of immune checkpoint blockade in advanced perivascular epithelioid cell neoplasms (PEComas): A retrospective single center study.

Abstract

11553 Background: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms with limited therapeutic options. While therapies targeting the mTOR pathway have shown promise, with nab-sirolimus being the first FDA-approved treatment for this histology, most patients will eventually progress. The role of immune checkpoint inhibitors (ICIs) remains poorly defined in these patients. Here, we present a retrospective analysis of PEComa patients treated with ICIs at Memorial Sloan Kettering Cancer Center (MSKCC). Methods: We retrospectively reviewed all patients with histologically confirmed PEComa treated with ICIs at MSKCC between 2016 and 2024. Patient demographics, disease characteristics, molecular profiles, treatment details, and clinical outcomes were collected. Endpoints included real-world progression-free survival (rwPFS), overall survival (OS), time on treatment (ToT) and response rate. Results: Thirteen patients with advanced PEComa received ICIs. The median age was 62 years (Range: 16-87), with 62% female patients. Primary tumor sites included uterus (n = 2), gastrointestinal tract (n = 4), soft tissue/extremities (n = 3), thyroid (n = 1), bladder (n = 1), renal (n = 1), and liver (n = 1). The most common molecular alterations identified were TFE3 fusions (23%), TSC1/TSC2 mutations (15%), TP53 alterations (46%) and ATRX mutations (46%). Patients received a median of 2 lines of previous therapies (range 1-6), with all patients receiving mTOR inhibitors (nab-Sirolimus in 46%). Most patients (78%) had previously received chemotherapy (gemcitabine and/or anthracycline, 54% each). ICIs included pembrolizumab (n = 5), nivolumab (n = 2), nivolumab-ipilimumab (n = 4), pembrolizumab-lenvatinib (n = 1) and nivolumab-bempegaldesleukin (n = 1). Median ToT was 1.6 months (95% CI: 0.9-NE) with 31% (95% CI 14-70%) remaining on treatment at 3 months. Median rwPFS was 3 months (95% CI: 1.4-NE) with a 6-month PFS of 38% (95% CI: 19-76%). Median OS was 26 months (95% CI: 4.13-NE) with a 12-month OS of 59% (95% CI: 37-95%). Partial responses were observed in three patients (23%), with two achieving durable responses exceeding 18 months (one on pembrolizumab and one on nivolumab-ipilimumab). These long-term responders subsequently underwent local interventions for oligoprogressive disease and remained progression-free at last follow-up. Molecular analysis of responders showed distinct profiles: one had TFE3 fusion, another had TP53 deletion and RB1 mutation, while the third had NOTCH1 and FLT4 mutations. Conclusions: The observed response rate of 23%, including two durable responses, suggests that ICIs may be an effective treatment option for a subset of PEComa patients, regardless of molecular profile. Further studies to identify predictive biomarkers and optimal sequencing with mTOR inhibitors and other therapies are warranted.