Overview

HHV-8 associated vascular malignancy. Four epidemiologic forms: AIDS-related (most common), classic (elderly Mediterranean), endemic (African), iatrogenic (transplant). HAART dramatically reduced AIDS-KS incidence. Treatment stratified by extent: local therapy (radiation, intralesional chemotherapy) for limited disease, systemic chemotherapy (liposomal doxorubicin, paclitaxel) for visceral or extensive cutaneous. Immune reconstitution cornerstone in AIDS-KS.

Clinical Management: Treatment individualized based on stage, histology, molecular profile, and patient factors. Multidisciplinary tumor board review recommended. Refer to NCCN guidelines and FDA package inserts for complete dosing and administration.

Epidemiology & Impact

Kaposi sarcoma is a vascular malignancy caused by human herpesvirus 8 (HHV-8/KSHV). Four epidemiologic forms exist: AIDS-associated (most common in Western countries), classic (elderly Mediterranean/Eastern European men), endemic (sub-Saharan Africa), and iatrogenic (transplant recipients). AIDS-associated KS has decreased dramatically with antiretroviral therapy but remains the most common AIDS-defining malignancy. The disease ranges from indolent skin lesions to aggressive visceral involvement.

Molecular Biology & Biomarkers

KS pathogenesis centers on HHV-8 infection, which encodes viral oncogenes including vFLIP (NF-kappaB activation), vCyclin (cell cycle bypass), and LANA (p53/Rb inhibition). The virus also produces viral IL-6 and vGPCR promoting angiogenesis. KS tumor cells have a mixed endothelial-mesenchymal phenotype. Immune suppression is critical for disease progression, explaining the association with HIV and immunosuppressive medications.

Kaposi sarcoma is caused by human herpesvirus-8 (HHV-8, also known as KSHV). The virus encodes several oncogenic proteins: vFLIP activates NF-ΞΊB, vCyclin drives cell cycle progression, and LANA maintains viral episomes and inhibits p53/RB. Viral IL-6 (vIL-6) promotes angiogenesis and inflammation. The KSHV-encoded G protein-coupled receptor (vGPCR) activates VEGF signaling, explaining the highly vascular nature of KS lesions. HIV-associated KS occurs in the setting of immune depletion, and immune reconstitution with antiretroviral therapy (ART) can lead to tumor regression. The PI3K/AKT/mTOR pathway is constitutively activated in KS, providing rationale for mTOR inhibitor use in transplant-associated KS.

Evolving Treatment Landscape

For AIDS-associated KS, antiretroviral therapy alone can induce tumor regression by restoring immune surveillance. Progressive or visceral disease requires liposomal doxorubicin as first-line systemic therapy (45-60% response). Paclitaxel is second-line. Pomalidomide has shown activity in resistant AIDS-KS. Checkpoint immunotherapy is being investigated cautiously. For transplant-associated KS, reduction of immunosuppression is the primary approach.

For HIV-associated KS, optimized antiretroviral therapy (ART) is the foundation of treatment and can lead to complete remission of limited disease. Systemic chemotherapy is indicated for advanced visceral disease, rapidly progressive KS, or immune reconstitution inflammatory syndrome (IRIS) KS. Pegylated liposomal doxorubicin (Doxil/Caelyx) is first-line, achieving response rates of 45-60%. Paclitaxel is an effective second-line agent. Pomalidomide is FDA-approved for AIDS-related KS after failure of ART and prior systemic therapy. For transplant-associated KS, switching from calcineurin inhibitors to sirolimus (mTOR inhibitor) can induce regression. Checkpoint inhibitors (pembrolizumab, nivolumab) have shown activity in clinical trials but require careful monitoring in HIV-positive and transplant populations.

Approved Kaposi Sarcoma Therapies

Doxil
pegylated liposomal doxorubicin
FDA Approved 1995 AIDS-related KS
Approved Indications (US/FDA)
Treatment of AIDS-related Kaposi sarcoma after failure of or intolerance to prior systemic chemotherapy.
Dosing Schedule
20 mg/mΒ² IV every 3 weeks
Drug Class
Anthracycline (Liposomal)
Manufacturer
Baxter/Janssen
Approval Year
1995
Key Publication
Northfelt et al. JCO 1998 β†—
Taxol
paclitaxel
FDA Approved 1997 AIDS-related KS
Approved Indications (US/FDA)
Second-line treatment of AIDS-related Kaposi sarcoma.
Dosing Schedule
135 mg/mΒ² IV over 3 hours every 3 weeks, or 100 mg/mΒ² IV every 2 weeks
Drug Class
Taxane (Antimicrotubular)
Manufacturer
Bristol-Myers Squibb
Approval Year
1997
Key Publication
Gill et al. JCO 1999 β†—
Pomalyst
pomalidomide
FDA Approved 2020 AIDS-related / Classic KS
Approved Indications (US/FDA)
Treatment of adult patients with AIDS-related KS after failure of highly active antiretroviral therapy (HAART), or in patients who are HIV-negative.
Dosing Schedule
5 mg orally once daily on Days 1-21 of 28-day cycle
Drug Class
Immunomodulatory Agent
Manufacturer
BMS/Celgene
Approval Year
2020
Pivotal Trial
NCT01495598 β†—
Key Publication
Polizzotto et al. JCO 2016 β†—