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- W3088659226 abstract "While the treatment of iatrogenic and HIV-related KS is well defined, mostly based on restoring the immune function, the treatment of classic/endemic KS is less codified. Chemotherapy or interferon are used for patients (pts) with extensive cutaneous and/or visceral KS but the tolerance may be poor in elderly pts, and long-term remissions are rare. Major efficacy of PD1 blockade has been demonstrated in Merkel cell carcinoma, another virus-induced tumor, in part driven by the immunogenicity of virus-associated antigens. Because of the involvement of HHV8 in KS and their good tolerance in older pts, the use of anti-PD1 appeared as a promising tool for classic/endemic KS. We conducted a multicenter single arm phase II trial in pts with classic/endemic KS with cutaneous extension requiring systemic treatment. Pts were treated with pembrolizumab (pembro) 200mg every 3 weeks for 6 months. Tumor assessment was performed by physical examination at each cycle (count, size, nodularity and color of target cutaneous lesions). The primary endpoint was the best overall response rate (BORR, ACTG criteria). A tumor response probability >30% using the Simon’s 2 stage optimal design was required to conclude that the drug was active. 17 pts (47% with classic and 53% with endemic KS) were included. 6 pts (35%) had lymph node extension. 12 pts (71%) were previously treated with chemotherapy. Median follow up was 25 weeks. Two pts had CR, 10 PR and 4 SD as best response (1 still on treatment; threshold of drug activity achieved). One pt discontinued treatment for toxicity. Treatment-related adverse events occurred in 11 pts (65%), including 1 grade 3 (6% - acute reversible cardiac decompensation). On baseline tumor samples, the lack of PDL1 expression on tumor and immune cells was associated with poor efficacy of pembro. The germline HLA-1 evolutionary divergence (HED) was determined for 16 pts. The 4 pts with SD as best response had significantly lower HED for HLA-B than pts with PR or CR. In the first prospective trial assessing the role of PD1 blockade in classic/endemic KS, pembro showed efficacy with 12 out of 16 of pts having CR or PR (BORR above 30%) and had an acceptable safety profile. If confirmed, this treatment could rapidly become standard of care." @default.
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- W3088659226 date "2020-09-01" @default.
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- W3088659226 title "1077MO PD1 blockade with pembrolizumab in classic and endemic Kaposi sarcoma: A multicenter phase II study" @default.
- W3088659226 doi "https://doi.org/10.1016/j.annonc.2020.08.1201" @default.
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