Tertiary lymphoid structures potential biomarker for pembrolizumab in STS

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The presence of tertiary lymphoid structures (TLS) in patients with advanced soft-tissue sarcomas (STS) may act as a potential predictive biomarker for treatment with pembrolizumab, potentially improving patient selection, according to a study.

Limited clinical activity has been demonstrated using immune checkpoint inhibitors in patients with advanced STS.

In the multicohort phase 2 study (PEMBROSARC) of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS,

A cohort of patients (n = 30) from the multicohort phase 2 study (PEMBROSARC) of pembrolizumab combined with low-dose cyclophosphamide, was selected based on the presence of TLSs.

In this cohort, the 6-month non-progression rate (NPR) and the objective response rate (ORR) were 40% and 30%, respectively compared to 4.9% and 2.4%, respectively, for cohorts in the PEMBROSARC trial enrolling all comers.

The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea, and anemia.

Further exploratory analyses found that the abundance of intratumoral plasma cells was significantly associated with improved outcomes.

Italiano A, Bessede A, Pulido M, et al. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat Med. 2022 May 26. doi: 10.1038/s41591-022-01821-3. Epub ahead of print. PMID: 35618839.