Teaching pack: Kaposi sarcoma

Kaposi sarcoma is a KSHV/HHV-8-driven vascular tumour with four epidemiologic forms: classic (elderly Mediterranean/Eastern European men, indolent), endemic African (including an aggressive lymphadenopathic childhood form), iatrogenic (transplant immunosuppression), and epidemic (AIDS-associated), plus KS in men who have sex with men with controlled HIV. Lesions involve skin, mucosa, lymph nodes and viscera (lung, gut); KSHV also causes primary effusion lymphoma and multicentric Castleman disease, and KS inflammatory cytokine syndrome (KICS).

AIDS-KS: antiretroviral therapy is the foundation and suffices for limited disease; advanced disease (visceral, oedema, rapid progression, T1 by ACTG staging) adds pegylated liposomal doxorubicin (first line) or paclitaxel, both approved in the 1990s; pomalidomide (2020) was the first new KS drug in two decades and works in HIV-positive and -negative patients. Iatrogenic KS responds to reducing immunosuppression or switching to mTOR inhibitors (sirolimus). Classic KS is treated with local therapy (radiotherapy, intralesional vincristine, cryotherapy) or the same systemic agents. In Africa, where paclitaxel is often unaffordable, bleomycin-vincristine regimens remain in use and ACTG A5263 showed paclitaxel superior to oral etoposide and BV. Immune checkpoint inhibitors show activity in small series.

• ART transformed AIDS-KS from a leading cause of death into a treatable condition in high-income countries; incidence fell >80% after 1996.
• Pomalidomide (2020) is the first new approved KS drug since 1997 and the first that also covers HIV-negative KS.
• Africa carries the burden: KS is a top-five cancer in many countries, and access to paclitaxel or liposomal doxorubicin is the limiting factor.
• Immunotherapy (PD-1) shows activity and is being tested; KSHV-targeted therapy remains investigational.

1. 1872Moritz Kaposi describes 'idiopathic multiple pigmented sarcoma of the skin'
2. 1981KS in young gay men heralds the AIDS epidemic (CDC MMWR)
3. 1994KSHV/HHV-8 discovered (Chang and Moore, Science)
4. 1995Liposomal doxorubicin approved for AIDS-KS
5. 1996Combination ART causes KS regression; incidence collapses
6. 1997Paclitaxel approved for AIDS-KS
7. 2020Pomalidomide approved for KS (HIV-positive and -negative)
8. 2020ACTG A5263: paclitaxel superior to oral etoposide and bleomycin-vincristine in Africa (Lancet)

• Pomalidomide (product)
• Pembrolizumab (product)
• Nivolumab (product)

• Access to effective chemotherapy and ART-linked cancer care in sub-Saharan Africa.
• KS in people with suppressed HIV and normal CD4 counts (unexplained).
• No antiviral therapy targets latent KSHV.
• Endemic childhood KS in Africa remains lethal.

1. What is the standard treatment for stage II-III triple-negative breast cancer today?
   Answer

   Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
2. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
3. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.

• NCCN Guidelines: Kaposi Sarcoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1447
• ACTG A5263 (Lancet 2020): https://doi.org/10.1016/S0140-6736(19)33222-2
• NCI PDQ: Kaposi sarcoma: https://www.cancer.gov/types/soft-tissue-sarcoma/patient/kaposi-treatment-pdq
• Wikipedia: https://en.wikipedia.org/wiki/Kaposi%27s_sarcoma
• Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1447