Kaposi's sarcoma, biologics and small molecules: Navigating the complex interplay between host immunity and viral biology. A case series with focused review of the literature

Abstract

The consequences of cytokine-specific immune modulation in the development and course of Kaposi's sarcoma (KS) are poorly understood. A retrospective chart review of patients treated with biologic/small molecule drugs and followed at the dedicated KS outpatient service of our Dermatology Unit was performed. The literature on biologic and small molecule drug use in KS patients was also reviewed. Data concerning 12 KS patients treated with biologic/small molecule drugs were collected. After a median delay of 6 months following biologic or small molecule drug introduction, nine patients experienced either KS onset or reactivation. Drugs associated with KS onset or flaring were: rituximab, infliximab, ruxolitinib apremilast (1), mirikizumab, abatacept (1). After a median follow-up of 25 months, all cases achieved persistent complete response through culprit drug discontinuation or drug withdrawal plus treatment. No effect on KS course was recorded with tocilizumab and vedolizumab.Based on our experience with the largest case series reported to date as well as the available literature, tocilizumab and ustekinumab seem to exert an overall neutral effect on KS. On the other hand, rituximab, infliximab, and ruxolitinib have been associated with the development or worsening of pre-existing KS and should be carefully pondered before use. Due to limited and partly controversial evidence, no definitive conclusions can be drawn on vedolizumab, apremilast, mirikizumab, abatacept.

Valganciclovir modulates the tumor necrosis factor axis molecules expression and CD4+ T-cell subsets in disseminated Kaposi Sarcoma patients

“…Clinically, it is presented with persistent fever, KS lesions exacerbation, edema, anemia, thrombocytopenia, and hypoalbuminemia, with a mortality rate of 60% [ 44 , 45 ]. According to this, in vitro studies have reported a relationship between the increased production of proinflammatory cytokines like TNF and the progression of KS [ 46 ]; however, it has been suggested that in vivo , TNF’s role in KS is complex and ambiguous [ 24 ].…”

“…Moreover, it has been proposed that PLWH have increased soluble TNF levels when they develop an exacerbated immune response [ 23 ]. However, understanding the TNF/TNFR’s axis role in KS is complex and still confusing [ 24 , 25 ]. Moreover, here is essential to mention that both TNF and TNFRs can be found in transmembrane (tm) or soluble (sol) form, and according to the form, they mediate a broad spectrum of cell functions from cell death to survival [ 26 ].…”

Iatrogenes Kaposi‐Sarkom unter Vedolizumab bei Colitis ulcerosa

“…Unter Berücksichtigung einer zusätzlich durchgeführten Literaturrecherche kam die Arbeitsgruppe zu dem Ergebnis, dass Rituximab, Infliximab (sowie andere TNF‐α‐Inhibitoren) und Ruxolitinib das Risiko für ein Rezidiv oder Neuauftreten eines KS erhöhen, während Tocilizumab und Ustekinumab einen eher neutralen Effekt zu haben scheinen. Zu Vedolizumab, Apremilast, Mirikizumab und Abatacept konnten aufgrund limitierter und teils widersprüchlicher Evidenz keine eindeutigen Schlussfolgerungen gezogen werden 2 …”

“…Bei drei Patienten, die Vedolizumab (n = 1) oder Tocilizumab (n = 2) erhielten, beeinflusste die Biologika‐Therapie den Verlauf eines bereits bestehenden KS nicht. Therapeutisch konnte bei allen Patienten durch Absetzen des auslösenden Medikamentes allein oder in Kombination mit einer lokalen Therapie oder Chemotherapie eine anhaltende komplette Remission erreicht werden 2 . Unter Berücksichtigung einer zusätzlich durchgeführten Literaturrecherche kam die Arbeitsgruppe zu dem Ergebnis, dass Rituximab, Infliximab (sowie andere TNF‐α‐Inhibitoren) und Ruxolitinib das Risiko für ein Rezidiv oder Neuauftreten eines KS erhöhen, während Tocilizumab und Ustekinumab einen eher neutralen Effekt zu haben scheinen.…”