Effectiveness and safety of conventional systemic treatments in classical and endemic Kaposi sarcoma: A multicentric retrospective study of 110 patients.
Authors: Grolleau Chloé , Walter-Petrich Anouk , Dupin Nicolas , Montlahuc Claire , Resche-Rigon Matthieu , Da Meda Laetitia , Le Cleach Laurence , Lebbe Celeste 
Published: June 2023

e21584

Background: Apart from post-transplant Kaposi sarcoma (KS), 2 major subtypes of non-HIV-related KS are described: classical Kaposi sarcoma (CKS) in patients originated from Mediterranean countries and endemic KS (EKS) in patients of sub-Saharan Africa origin. Some patients with aggressive EKS or CKS require systemic treatments among which liposomal anthracycline (LA), taxanes and, to a lesser extent, low dose interferon (LDI) are generally recommended as first lines. Recently, anti-PD1 have shown promising results in an early phase II trial. At the dawn of a turning point in therapeutic era, we aim to map the effectiveness and safety of the main conventional systemic treatments usually available in KS. Methods: We performed a national multicentric retrospective study including all patients receiving a systemic treatment for a histologically proven KS between January 1st 2013 to July 1st 2019. HIV infected patients and patients treated with immunosuppressive drugs were excluded. Overall response was defined as a decrease of more than 50% of lesion area and serious adverse events encompassed grade 3 and 4 toxicity. Results: A total of 110 patients were included. Sixty-nine had CKS (62.7%) and 41 had EKS (37.2) with a median age at diagnosis of 69 (IQR: 57-77) and 41 years (37-59) (p = 0.011), respectively. At the time of diagnosis, EKS was associated with greater systemic involvement compared with CKS (36.6% vs 14.9%, p = 0.017). First-line therapy was initiated within a median of 13.8 months (2.9-43) after KS diagnosis. The 3 main regimens were taxanes (27.3%), LA (19.1%) and LDI (19.1%) with response rates of 82.8%, 80% and 52.6% (p = 0.063), respectively. The cumulative incidence of a second line of treatment in the first 2 years of follow-up was 49.5% (CI95% 38.7-59.4), without significant difference according to the different regimens. Toxicity, regardless of grade, was reported more frequently with LDI (55.3%) and taxanes (47.8%) than with LA (30.4%) (p = 0.035). Poor tolerability led to discontinuation of LDI more frequently than LA (OR = 4.17, p = 0.048), without difference for taxanes. There was no difference in serious adverse events between the 3 main regimens. CKS and EKS didn’t differ regarding overall response rate or time to next treatment regardless of treatment regimens. However, response rates tended to decrease as the lines went on for EKS (from 77.5% in 1st to 33.3% in 3rd line, p = 0.005), in contrast to CKS who maintained a sustained response, with more frequent systemic involvement (56% vs 25.4%, p = 0.002) during EKS course. Conclusions: Herein, we highlight LA, taxanes and LDI are safe and effective treatments for non-immunodeficient KS. Furthermore, EKS differed from CKS, occurring in younger patients, with more frequent systemic involvement and response loss through therapeutic lines, emphasizing the need to evaluate new agents in this form of KS.