Treatment of Kaposi sarcoma with immune-checkpoint inhibitors: A systematic review and single-arm meta-analysis

Kaposi sarcoma (KS) is a rare cutaneous tumor of endothelial origin, caused by human herpesvirus type 8. Chemotherapy is the standard treatment for KS patients with extensive cutaneous or visceral disease. However, long-term remission is rare. Early phase studies of immune checkpoint inhibitors (ICI) in KS patientshave demonstrated acceptable safety and efficacy profiles. We conducted a systematic review and meta-analysis of efficacy and safety of ICI in patients with KS. We searched for clinical trials and observational cohort studies assessing KS patients treated with ICI on PubMed, Scopus, the Cochrane Library, ASCO publications, ESMO, and AACR databases. Efficacy was measured as best overall response rate (BORR), which is defined as the proportion of patients who have a partial (PR) or complete response (CR) to therapy. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values < 0.05 and I(2) > 25% were considered significant for heterogeneity. We used a DerSimonian and Laird random effects model. We included five studies: four phase I/II clinical trials and one observational retrospective cohort, for a total of 65 patients. Thirty (46%) patients were HIV-positive, 26 (40%) had classical KS, and 9 (14%) endemic KS. Fifty-six (86%) had previously received at least one systemic treatment for KS. Forty-seven (72%) received single agent anti-PD1 and 18 (28%) the combination of nivolumab 240 mg d1, d15, d28 and ipilimumab 1mg/kg d1 q.42 days. In a pooled analysis, BORR was 58% (95% CI 39 - 77%). Five patients achieved CR, 32 had PR and 2 had sustained stable disease for 24 months. Patients with classic and endemic KS had a BORR of 74% (95% CI 60 - 89%) with a follow-up of >20 months. HIV-related KS patients had a BORR of 44% (95% CI 22 - 65%) with a follow-up range of 3.7 to 5 months. Grade 3 or 4 toxicity were reported in 6/44 patients (13.6%). One patient died of KS herpesvirus associated polyclonal B-cell proliferation. This single-arm meta-analysis confirms that ICI has anti-tumor activity in patients with KS. Other studies are ongoing and may shed more light on the activity of ICI in KS. Larger phase 3 studies with longer follow up are warranted.