(P 235) AGNOSTIC INDICATION OF IMMUNE CHECKPOINT INHIBITORS (ICI): PATTERNS OF RESPONSE OF SARCOMAS

Objective: The ICI pembrolizumab is approved for solid tumors with high tumor mutational burden (TMB), mismatch repair deficient status (dMMR), and/or microsatellite stability-high status (MSI-H). Recent data indicate high response rates and prolonged response duration in carcinomas, but scant data exist for sarcomas with those features. This study describes our single-center experience with ICI in sarcomas characterized by high TMB, dMMR status and/or MSI-H.

Methods: A retrospective analysis of patients’ charts was authorized by the Institutional Review Board. Eligible case criteria: age >18; any sarcoma subtype; tumor demonstrating at least one of the following by NGS: high TMB ( >10 mutations/Mb), dMMR and/or MSI-H. Receipt of ICI was required. We retrieved the following data for analysis: date of initiation/termination of ICI treatment; best response observed per RECIST criteria; response duration.

Results: 11 patients (6 M/5 F) met the inclusion criteria. They were aged 34-73 at the time of diagnosis. The following histologies were represented: leiomyosarcoma (3), undifferentiated pleomorphic sarcoma (UPS) or unclassified high-grade sarcoma (2); malignant peripheral nerve sheath tumor (MPNST) (2), angiosarcoma (2); pleomorphic dermal sarcoma (PDS) (1), extra-skeletal osteosarcoma (ESO) (1 ). TMB ranged from 10.5 to 151 mutations/Mb. 2 patients have just started treatment with pembrolizumab. 9 patients for now are evaluable: 7 received single-agent pembrolizumab, 1 pembrolizumab/eribulin, and 1 ipilimumab/nivolumab. 3/9 (33%) patients experienced objective response (1 CR cutaneous angiosarcoma, 1 CR PDS, 1 PR UPS ). 2 patients experienced stable disease as their best outcome: 1 extra-skeletal osteosarcoma , 1 leiomyosarcoma. Finally, upfront progression was seen in the remaining 4 patients (2 leiomyosarcomas, 1 MPNST, 1 UPS). For the 3 responders, the duration of response ranged from 8 months (UPS) to 18 months (PDS), with 1 patient (cutaneous angiosarcoma) presently in CR at 6 months of on an ongoing treatment. Toxicity was consistent with previously published reports. Updated results will be presented at the conference.

Conclusion: Although high TMB, dMMR and MSI-H status are uncommon in sarcomas, this small series suggests these cases can benefit from ICI. However, the best responses were observed in subtypes known to benefit from ICI regardless of their biomarker status. A larger study is needed to evaluate the predictive value of high TMB, dMMR, and MSI-H status across sarcoma subtypes.