What is Kaposi's sarcoma?

From the Guidelines

Kaposi sarcoma treatment should prioritize antiretroviral therapy (ART) for HIV-associated cases, with the addition of systemic chemotherapy, such as liposomal doxorubicin, for advanced or symptomatic disease. The management of AIDS-related Kaposi sarcoma depends on the location and extent of the disease, as well as the patient's immune status 1. For patients with limited cutaneous disease that is asymptomatic and cosmetically acceptable, treatment with ART alone may be sufficient, as optimization of immune function and HIV viral suppression can lead to remissions or stable disease 1.

Treatment Options

• For symptomatic and/or cosmetically unacceptable limited cutaneous disease, treatment with ART and minimally invasive therapies, such as topical treatments, intralesional chemotherapy, radiation, or local excision, is recommended 1.
• For advanced cutaneous, oral, visceral, or nodal AIDS-related Kaposi sarcoma, the preferred initial treatment is ART with clinical trial or systemic therapy, such as liposomal doxorubicin 1.
• Liposomal doxorubicin is associated with a risk of cardiotoxicity, and a baseline echocardiogram should be performed before initial and repeat courses, with a lifetime dose limited to 400 to 450 mg/m² 1.

Systemic Therapy

• The preferred first-line systemic therapy for both limited cutaneous disease and advanced disease is liposomal doxorubicin, with an overall response rate of 46% and a median time to treatment failure of approximately 4 months 1.
• An alternative option for first-line systemic therapy is paclitaxel, which has significant activity in the advanced disease setting, with neutropenia as the most frequent dose-limiting toxicity 1.

Surveillance and Relapse

• Surveillance of patients treated for AIDS-related Kaposi sarcoma is important, as disease can recur after an initial complete response, and persistence of HHV-8 and emergence of distinct tumor clones can lead to disease progression and relapse 1.
• For relapsed/refractory disease, a typical systemic therapy sequence would be first-line liposomal doxorubicin, followed by second-line paclitaxel, and then pomalidomide in the third line of treatment 1.

From the FDA Drug Label

The efficacy of paclitaxel was evaluated by assessing cutaneous tumor response according to the amended ACTG criteria and by seeking evidence of clinical benefit in patients in 6 domains of symptoms and/or conditions that are commonly related to AIDS-related Kaposi’s sarcoma Cutaneous Tumor Response (Amended ACTG Criteria): The objective response rate was 59% (95% CI, 46 to 72%) (35 of 59 patients) in patients with prior systemic therapy. The median time to response was 8.1 weeks and the median duration of response measured from the first day of treatment was 10.4 months (95% CI, 7.0 to11. 0 months) for the patients who had previously received systemic therapy.

Kaposi Sarcoma Treatment with Paclitaxel:

• The objective response rate to paclitaxel in patients with AIDS-related Kaposi's sarcoma was 59% in patients with prior systemic therapy.
• The median time to response was 8.1 weeks.
• The median duration of response was 10.4 months.
• Paclitaxel may provide clinical benefit in patients with Kaposi’s sarcoma, including improved pulmonary function, ambulation, resolution of ulcers, and decreased analgesic requirements.
• Patients with AIDS-related Kaposi’s sarcoma may have more severe hematologic toxicities than patients with solid tumors, and require a lower dose intensity and supportive care 2.
• The use of supportive therapy, including G-CSF, is recommended for patients who have experienced severe neutropenia 2.

From the Research

Definition and Prevalence of Kaposi Sarcoma

• Kaposi sarcoma (KS) is a malignancy associated with Kaposi's sarcoma-associated herpesvirus (KSHV), primarily affecting immunocompromised individuals, such as those with HIV or those receiving immunosuppressive treatments 3.
• KS is the most common malignancy associated with HIV infection and is considered an AIDS-defining condition by the US Centers of Disease Control Guidelines 4.
• The disease manifests in different forms, including classic, endemic, epidemic, iatrogenic, and in men having sex with men, each with distinct clinical features depending on immune status and geographic area of origin 3.

Treatment Options for Kaposi Sarcoma

• Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression 5.
• In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative 5.
• HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma 6, 7.
• Promising emerging therapies, including immunomodulatory agents, antiangiogenic therapies, and checkpoint inhibitors, are also being explored 3.

Diagnosis and Staging of Kaposi Sarcoma

• The role of histology, immunohistochemistry, and staging in diagnosing KS and assessing disease extension is crucial 3.
• Other KSHV diseases, such as multicentric Castelman disease, primary effusion lymphoma, and KS inflammatory cytokine syndrome, should also be considered in the diagnosis and treatment of KS 3.

Management and Outcomes of Kaposi Sarcoma

• Effective management of KS remains a challenge, and personalized treatment based on the patient's underlying condition and KS subtype is essential 3.
• The review emphasizes the importance of a comprehensive approach to investigating and treating KS, including restoring immunity in immunocompromised patients, alongside conventional local therapies, and chemotherapy options for aggressive and extensive forms 3.