Oncologic Treatment of HIV-Associated Kaposi Sarcoma 40 Years on

Abstract

The observation in 1981 of the emergence of Kaposi sarcoma (KS) among young men who had sex with men was one of the first harbingers of the HIV epidemic. With advances in HIV care, the incidence of HIV-associated KS (HIV⁺KS) has decreased over time in the United States. However, it remains a persistent malignancy among some HIV-infected populations and is one of the most common tumors in sub-Saharan Africa. Because of the relapsing and remitting nature of this cancer, patients with HIV⁺KS can experience significant, long-term, morbidity. Patients with severe HIV⁺KS may also have concurrent lymphoproliferative syndromes, malignancies, and/or infections that can contribute to mortality. Several chemotherapy agents were explored in clinical trials for HIV⁺KS during the early stage of the epidemic. As HIV⁺KS emerges with CD4 lymphopenia and immunodysregulation, T-cell-sparing options are important to consider. Here, we explore the pathogenesis of HIV⁺KS and the current evidence for immunotherapy and therapies that potentially target KS pathogenesis. This review provides the current landscape of therapies for HIV⁺KS and highlights management issues for patients with HIV and cancer.

FIG 1.

KS lesions in selected clinical trial participants at study entry. The images are nonidentifiable to protect patient privacy. KS, Kaposi sarcoma.

FIG 2.

Oncologic and HIV workup of patients with HIV-associated KS. Patients who present with systemic symptoms or multiorgan dysfunction may have other concurrent KSHV-associated conditions. Therefore, in addition to an infectious workup, additional diagnostic procedures may be required depending on the extent of symptoms and degree of immunosuppression as this will influence management. Created using BioRender. CT, computed tomography; KS, Kaposi sarcoma; KSHV, Kaposi sarcoma herpesvirus; MCD, multicentric Castleman disease; PEL, primary effusion lymphoma; PET, positron emission tomography; VL, viral load.

FIG 3.

Staging and treatment strategy for KS and other KSHV-associated diseases. With respect to staging, I stage may have less prognostic value than T or S stages in the current era with ART. B symptoms are unexplained fever, night sweats, or > 10% weight loss. KS can occur with MCD, PEL, and KICS. Patients with PEL may also meet criteria for KICS. Diagnosis of a concurrent KSHV-associated diseases will affect therapy and long-term outcomes. First- and second-line therapies for KS are from FDA approval and NCCN guidelines. Treatments noted for PEL and MCD with concurrent KS are based on NCCN guidelines. ^aOverall good risk is defined as T0S0, T1S0, and T0S1, whereas overall poor risk is T1S1. ^bSystemic therapy includes treatment approved for HIV⁺KS such as chemotherapy (liposomal doxorubicin, paclitaxel) or immunomodulatory therapy (pomalidomide). ^cFor patients with recurrent and/or persistent disease, consider evaluation for concurrent KSHV-associated processes. Created using BioRender. ART, antiretroviral therapy; CHOP, cyclophosphamide, doxorubicin, vincristine and prednisone; EPOCH, etoposode, prednisone, vincristine, cyclophosphamide, doxorubicin; FDA, US Food and Drug Administration; HIV⁺KS, HIV-associated Kaposi sarcoma; IL, interleukin; KICS, KSHV-associated inflammatory cytokine syndrome; KS, Kaposi sarcoma; KSHV, Kaposi sarcoma herpesvirus; LD, liposomal doxorubicin; MCD, multicentric Castleman disease; NCCN, National Comprehensive Cancer Network; PEL, primary effusion lymphoma.