General Information About Kaposi Sarcoma

Epidemiology

Kaposi sarcoma (KS) was first described in 1872 by the Hungarian dermatologist, Moritz Kaposi. From that time until the HIV and AIDS epidemic, KS remained a rare tumor. Classic KS is most commonly seen in Europe and North America in older men of Italian or Eastern European Jewish ancestry,[1] and endemic KS is most commonly seen in sub-Saharan Africa. The disseminated, fulminant form of KS associated with HIV disease is referred to as AIDS-associated KS to distinguish it from classic and endemic KS. Transplant-related KS (also sometimes called iatrogenic KS) is seen in patients receiving chronic immunosuppression therapy, such as after organ transplant.[2,3]

Histopathology

Although the histopathology of the different types of KS is essentially identical, the clinical manifestations and course of the disease differ dramatically.[2] Human herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus, was identified in KS tissue biopsies from almost all patients with classic, endemic, AIDS-associated, and transplant-related KS but was absent from noninvolved tissue.[2]

Classic Kaposi Sarcoma

Classic KS is considered a rare disease. It occurs more often in men, at a ratio of approximately 10 to 15 men to 1 woman. In North American and European populations, the usual age at onset is between 50 and 70 years. Classic KS tumors usually present with one or more asymptomatic red, purple, or brown patches, plaques, or nodular skin lesions. The disease is often limited to single or multiple lesions usually localized to one or both lower extremities, especially involving the ankles and soles.

Classic KS most commonly runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesions. Venous stasis and lymphedema of the involved lower extremity are frequent complications. In long-standing cases, systemic lesions can develop along the gastrointestinal tract, in lymph nodes, and in other organs. The visceral lesions are generally asymptomatic and are most often discovered only at autopsy, though clinically, gastrointestinal bleeding can occur. As many as 33% of patients with classic KS develop a second primary malignancy, which is most often non-Hodgkin lymphoma.[4]

Endemic Kaposi Sarcoma

Endemic KS refers to KS diagnosed in patients, typically children and younger adults, living in sub-Saharan Africa. This classification was based on several reports from the 1950s of KS in this younger HIV-negative cohort in human herpesvirus–endemic African countries. Prior to the AIDS epidemic, the estimated incidence for endemic KS was highest (>6 per 1,000 person-years) in Uganda, Tanzania, Cameroon, and Congo. The etiology behind endemic KS is unclear but may possibly be related to saliva-sharing practices, chronic infection, and malnutrition.[3]

The clinical presentation of endemic KS varies and differs between children and adults. Whereas adults present with disease that resembles classic KS, children can have more aggressive disease, including diffuse lymphadenopathy, significant lymphedema, and visceral dissemination.[3]

AIDS-Associated Kaposi Sarcoma

The use of antiretroviral therapy for patients with AIDS-associated KS has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[5,6,7] Antiretroviral therapy has delayed or prevented the emergence of drug-resistant HIV strains, profoundly decreased viral load, led to increased survival, and lessened the risk of opportunistic infections.[8] KS can still appear during antiretroviral therapy with complete suppression of HIV; most cases in the United States occur in patients with high CD4 counts receiving ongoing antiretroviral therapy.[9]

The disease often progresses in an orderly fashion from a few localized or widespread mucocutaneous lesions that may involve the skin, oral mucosa, and lymph nodes to more numerous lesions and generalized skin disease that involves visceral organs, such as the gastrointestinal tract, lung, liver, and spleen. Most patients with HIV disease who present with mucocutaneous KS lesions feel healthy and are usually free of systemic symptoms, as compared with HIV patients who first develop an opportunistic infection. AIDS-associated KS presents at sites that are much more varied than those seen in other types of this neoplasm. While most patients present with skin disease, KS involvement of lymph nodes or the gastrointestinal tract may occasionally precede the appearance of the cutaneous lesions.

Transplant-Related Kaposi Sarcoma

Transplant-related KS (also called iatrogenic KS) is diagnosed in patients who are therapeutically immunosuppressed, such as after an organ transplant. In fact, solid-organ transplant recipients are 200-fold more likely to develop KS than the general population. Risk factors include male sex, older age, higher levels of immune suppression, and living in HHV8-endemic areas.[3]

Transplant-related KS typically yields cutaneous lesions, though mucosal and visceral disease can occur. The lesions commonly occur within the first several months of immunosuppression therapy and regress with changes or reductions in immunosuppression.[3]

References:

1. Ruocco E, Ruocco V, Tornesello ML, et al.: Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies. Clin Dermatol 31 (4): 413-422, 2013 Jul-Aug.
2. Uldrick TS, Whitby D: Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Lett 305 (2): 150-62, 2011.
3. Cesarman E, Damania B, Krown SE, et al.: Kaposi sarcoma. Nat Rev Dis Primers 5 (1): 9, 2019.
4. Safai B, Good RA: Kaposi's sarcoma: a review and recent developments. Clin Bull 10 (2): 62-9, 1980.
5. Portsmouth S, Stebbing J, Gill J, et al.: A comparison of regimens based on non-nucleoside reverse transcriptase inhibitors or protease inhibitors in preventing Kaposi's sarcoma. AIDS 17 (11): F17-22, 2003.
6. Carrieri MP, Pradier C, Piselli P, et al.: Reduced incidence of Kaposi's sarcoma and of systemic non-hodgkin's lymphoma in HIV-infected individuals treated with highly active antiretroviral therapy. Int J Cancer 103 (1): 142-4, 2003.
7. Grabar S, Abraham B, Mahamat A, et al.: Differential impact of combination antiretroviral therapy in preventing Kaposi's sarcoma with and without visceral involvement. J Clin Oncol 24 (21): 3408-14, 2006.
8. Lodi S, Guiguet M, Costagliola D, et al.: Kaposi sarcoma incidence and survival among HIV-infected homosexual men after HIV seroconversion. J Natl Cancer Inst 102 (11): 784-92, 2010.
9. Yanik EL, Achenbach CJ, Gopal S, et al.: Changes in Clinical Context for Kaposi's Sarcoma and Non-Hodgkin Lymphoma Among People With HIV Infection in the United States. J Clin Oncol 34 (27): 3276-83, 2016.

Stage Information and Response Evaluation for Kaposi Sarcoma

Staging

The staging evaluation of patients with classic Kaposi sarcoma (KS) should be individualized. The advanced age of most patients, localized nature of the tumor, rarity of visceral involvement, and usually indolent course of the disease should temper the extent of the evaluation. A careful examination of the skin and lymph nodes is sufficient in most cases.

For the rare patient with a rapidly progressive tumor or signs or symptoms of visceral involvement, appropriate evaluation is indicated. No universally accepted classification is available for AIDS-associated KS. Staging schemes that incorporate laboratory parameters as well as clinical features have been proposed. Since most patients with AIDS-associated KS do not die of the disease, factors besides tumor burden are apparently involved in survival.

The conventions used to stage KS and the methods used to evaluate the benefits of KS treatment continue to evolve because of changes in the treatment of HIV and in recognition of deficiencies in standard tumor assessment. The clinical course of KS, the selection of treatment, and the response to treatment are heavily influenced by the degree of underlying immune dysfunction and opportunistic infections.

The AIDS Clinical Trials Group (ACTG) Oncology Committee has published criteria for the evaluation of AIDS-associated KS.[1] The staging system incorporates measures of extent of disease, severity of immunodeficiency, and presence of systemic symptoms. As shown in Table 1 below, the ACTG criteria categorize the extent of the tumor as localized or disseminated, the CD4 cell number as high or low, and systemic illness as absent or present.

A subsequent prospective analysis of 294 patients entered on ACTG trials for KS between 1989 and 1995 showed that each of the tumor (T), immune system (I), and systemic illness (S) variables was independently associated with survival.[2] Multivariate analysis showed that immune system impairment was the most important single predictor of survival. In patients with relatively high CD4 counts, tumor stage was predictive. A CD4 count of 150 cells/µL may be a better discriminator than the published cutoff of 200 cells/µL. A study is under way to determine if quantifying viral load adds predictive value. None of the previous studies were conducted at a time when antiretroviral therapy was readily available. The impact of antiretroviral therapy on survival in KS requires continued assessment.

Response Evaluation

The ACTG proposed a unified treatment response evaluation system for AIDS-related KS for clinical practice and research.[1] After appropriate clinical examination and relevant interval imaging or endoscopy, patients are characterized as having complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), based on the following criteria:

• CR: No detectable residual disease and no tumor-related edema for at least 4 weeks.
• PR: No new mucocutaneous lesions, visceral disease, or worsening tumor-related edema. Existing sites show a 50% reduction in (1) the number of lesions, (2) the form of lesions (i.e. flattening of raised lesions), and/or (3) the sum of the products of the largest perpendicular diameters of five measurable lesions. If residual tumor-related edema is present despite meeting CR criteria, the response is still characterized as a PR.
• PD: Increase of more than 25% in (1) the size of existing lesions and/or (2) the number of existing lesions that have more nodular or plaque-like form, or the development of new sites of disease.
• SD: No PR, CR, or PD.

References:

1. Krown SE, Metroka C, Wernz JC: Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 7 (9): 1201-7, 1989.
2. Krown SE, Testa MA, Huang J: AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 15 (9): 3085-92, 1997.

Treatment of Classic and Endemic Kaposi Sarcoma

Classic Kaposi sarcoma (KS), as well as endemic KS in adult patients, is usually limited to the skin and has an indolent course. Thus, management for both is typically similar. Patients are predisposed to develop a second primary malignancy, and the treating physician should consider this factor when arranging a schedule of follow-up treatment for the patient.

Treatment Options for Localized Classic and Endemic Kaposi Sarcoma

Treatment options for localized skin disease include the following (options are equivalent):

1. Radiation therapy.
2. Surgery.
3. Other options (cryo-laser, intralesional, and topical therapy).

Radiation therapy

For solitary lesions or lesions of limited extent, modest doses of radiation applied with a limited margin provide excellent control of disease in the treated area. Usually, superficial radiation beams, such as electron beams, are used. Some authors believe disease recurrence in adjacent untreated skin is common if only involved-field radiation therapy is used and claim better cure rates when extended-field radiation therapy is used.[1]

For low-voltage (100 kv) photon radiation therapy, 8 Gy to 10 Gy is given as a single dose or 15 Gy to 20 Gy is given over 1 week because solitary lesions control nearly 100% of local disease, but recurrence in adjacent areas is common.

For electron-beam radiation therapy (EBRT), 4 Gy is given once weekly for 6 to 8 consecutive weeks with a 4-MeV to 6-MeV electron beam. Ports should include the entire skin surface 15 cm above the lesion.

Surgery

Surgical excision may benefit patients with small superficial lesions, but local recurrence is likely to occur. However, multiple small excisions can continue to be performed for good disease control.

Other options

Based on extent and accessibility of lesions, alternate modalities such as cryo-, laser, intralesional, and topical therapy can be used. Use of these modalities is based on evidence extrapolated from treatment of AIDS-associated KS.[2,3]

Treatment Options for Advanced Classic and Endemic Kaposi Sarcoma

Treatment options for advanced skin disease include the following:

1. Radiation therapy.
2. Chemotherapy.
3. Biological and targeted therapy.
4. Immunotherapy.

Radiation therapy

Modest doses can be effective in controlling widespread skin disease. The type of radiation (i.e., photon vs. electron) and fields used must be tailored to suit the distribution of disease in the individual patient.[1] Radiation therapy options include the following:

• Extended-field EBRT.
• For disease limited to areas distal to the knee, subtotal-skin EBRT directed to skin below the umbilicus.
• For disease that extends above the knee, total-skin EBRT.

  EBRT used in this manner gave long-term results that were superior to those obtained with radiation therapy administered to successive individual lesions as they appeared.[4]

• For extensive disease, EBRT 4 Gy given once weekly for 6 to 8 consecutive weeks, and subtotal- or total-skin radiation therapy.

Chemotherapy

Because classic KS is such a rare disease in the United States, and is usually treated initially with radiation therapy, few patients have been treated with chemotherapy. Its use in classic KS is based on data extrapolated from treatment of AIDS-associated KS, and no randomized prospective trials have compared one agent with another in classic KS. The agents listed below have potential benefit.

Pegylated liposomal doxorubicin (PLD)

PLD has shown activity in several case series and single-institution analyses.[5,6,7,8]

Evidence (PLD):

1. A multicenter trial included 55 patients with classic KS who were treated over a decade.[5]
   • A 71% overall response rate was seen using PLD, with a median response duration of 25 months.[5][Level of evidence C3]

Taxanes

Paclitaxel has shown activity in both AIDS-associated and classic KS in small case series.[9,10,11,12]

Evidence (taxanes):

1. A small trial included 73 patients with AIDS-associated KS (32% had an undetectable HIV viral load). Patients were randomly assigned to receive either PLD or paclitaxel.[9]
   • Response rates were 46% for patients who received PLD and 56% for patients who received paclitaxel. The median progression-free survival (PFS) was 12 months for patients who received PLD and 18 months for patients who received paclitaxel. The 2-year overall survival rates were 78% for patients who received PLD and 79% for patients who received paclitaxel.[9][Level of evidence B3]

Other chemotherapy agents

Single-agent vinblastine [13,14,15,16], oral etoposide [17,18,19], and gemcitabine [20,21,22] have all shown good activity in classic and AIDS-associated KS.

Evidence (other chemotherapy agents):

1. A phase III trial included 65 patients with classic KS. Patients were randomly assigned to receive either oral etoposide or vinblastine.[18]
   • Response rates were relatively high and did not significantly differ (58% for patients who received PLD and 74% for patients who received paclitaxel).[18][Level of evidence B3]

Biological and targeted therapy

Agents that modulate the immune system, such as imide drugs and interferon alfa-2b, have shown efficacy in both classic and AIDS-associated KS.

Pomalidomide

Pomalidomide has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of KS in patients with and without HIV.

Evidence (pomalidomide):

1. A phase I/II study of pomalidomide included 28 patients with KS. Ten patients were HIV-positive and 18 patients were HIV-negative.[23]
   • The overall response rate was 71%, and 80% among patients without HIV. The median PFS was 10 months.[23]
   • Pomalidomide was generally well tolerated. Common adverse events included neutropenia, anemia, fatigue, constipation, and rash. There were few grade 3 events (neutropenia, infection, and edema).[24]

Pomalidomide is teratogenic, prescribed through a Risk Evaluation and Mitigation Strategy (REMS) program, and it should be given with aspirin to mitigate venous thromboembolism risk.

Interferon alfa-2b

Interferon alfa-2b is approved by the FDA for treatment of AIDS-associated KS. It is sometimes used off-label for classic KS.

Evidence (interferon alfa-2b):

1. A small case series included 16 patients without HIV.[25]
   • Treatment with interferon alfa-2b led to a response in ten patients (one complete response [CR], nine partial responses [PRs]).

Immunotherapy

Immune checkpoint inhibitor therapy has been tested in classic KS and yielded promising results.

Pembrolizumab monotherapy

Evidence (pembrolizumab monotherapy):

1. Pembrolizumab monotherapy (given every 3 weeks for up to 6 months) was evaluated in a multicenter, single-arm, phase II study of 17 patients. Eight patients had classic KS and nine patients had endemic KS.[26][Level of evidence C3]
   • At a median follow-up of 20.4 months, with 88% of patients completing 6 months of treatment, the best overall response rate was 71% (12% with CR, 59% with PR). An additional 29% of patients had stable disease based on AIDS Clinical Trials Group response evaluation.
   • The median time to response was 5 months (interquartile range, 3.4–12), the estimated median duration of response was 23 months (95% confidence interval [CI], 21.2–not reached [NR]), and the median time to progression (TTP) was 24 months (95% CI, 15–NR).
   • Sixty-four percent (7 of 11) of pretreated patients and 83% (5 of 6) of chemotherapy-naïve patients had a CR or PR.
   • Pembrolizumab was generally well tolerated. Two patients (12%) had grade 3 events: acute cardiac decompensation and granulomatous reaction in the lung. Two patients discontinued treatment due to grade 2 pancreatitis and grade 3 acute cardiac decompensation, respectively.

Ipilimumab and nivolumab

Evidence (ipilimumab and nivolumab):

1. Ipilimumab and nivolumab combination therapy was evaluated in a phase II study of 18 patients with refractory classic KS. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression, for up to 24 months.[27]
   • At a median follow-up of 24.4 months, the overall response rate was 87% by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The 6- and 12-month PFS rates were 77% and 59%, respectively.[27][Level of evidence B4]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Tsao MN, Sinclair E, Assaad D, et al.: Radiation therapy for the treatment of skin Kaposi sarcoma. Ann Palliat Med 5 (4): 298-302, 2016.
2. Epstein JB, Lozada-Nur F, McLeod WA, et al.: Oral Kaposi's sarcoma in acquired immunodeficiency syndrome. Review of management and report of the efficacy of intralesional vinblastine. Cancer 64 (12): 2424-30, 1989.
3. Bodsworth NJ, Bloch M, Bower M, et al.: Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's sarcoma. Am J Clin Dermatol 2 (2): 77-87, 2001.
4. Nisce LZ, Safai B, Poussin-Rosillo H: Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma. Cancer 47 (4): 640-4, 1981.
5. Di Lorenzo G, Kreuter A, Di Trolio R, et al.: Activity and safety of pegylated liposomal doxorubicin as first-line therapy in the treatment of non-visceral classic Kaposi's sarcoma: a multicenter study. J Invest Dermatol 128 (6): 1578-80, 2008.
6. Castiñeiras I, Almagro M, Rodríguez-Lozano J, et al.: Disseminated classic Kaposi's sarcoma. Two cases with excellent response to pegylated liposomal doxorubicin. J Dermatolog Treat 17 (6): 377-80, 2006.
7. Di Lorenzo G, Di Trolio R, Montesarchio V, et al.: Pegylated liposomal doxorubicin as second-line therapy in the treatment of patients with advanced classic Kaposi sarcoma: a retrospective study. Cancer 112 (5): 1147-52, 2008.
8. Potouridou I, Korfitis C, Ioannidou D, et al.: Low to moderate cumulative doses of pegylated liposomal doxorubicin in the treatment of classic Kaposi sarcoma in elderly patients with comorbidities. Br J Dermatol 158 (2): 431-2, 2008.
9. Cianfrocca M, Lee S, Von Roenn J, et al.: Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer 116 (16): 3969-77, 2010.
10. Brambilla L, Romanelli A, Bellinvia M, et al.: Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases. Br J Dermatol 158 (6): 1339-44, 2008.
11. Chao SC, Lee JY, Tsao CJ: Treatment of classical type Kaposi's sarcoma with paclitaxel. Anticancer Res 21 (1B): 571-3, 2001.
12. Fardet L, Stoebner PE, Bachelez H, et al.: Treatment with taxanes of refractory or life-threatening Kaposi sarcoma not associated with human immunodeficiency virus infection. Cancer 106 (8): 1785-9, 2006.
13. Solan AJ, Greenwald ES, Silvay O: Long-term complete remissions of Kaposi's sarcoma with vinblastine therapy. Cancer 47 (4): 637-9, 1981.
14. Tucker SB, Winkelmann RK: Treatment of Kaposi sarcoma with vinblastine. Arch Dermatol 112 (7): 958-61, 1976.
15. Scott WP, Voight JA: Kaposi's sarcoma. Management with vincaleucoblastine. Cancer 19 (4): 557-64, 1966.
16. Klein E, Schwartz RA, Laor Y, et al.: Treatment of Kaposi's sarcoma with vinblastine. Cancer 45 (3): 427-31, 1980.
17. Tas F, Sen F, Keskin S, et al.: Oral etoposide as first-line therapy in the treatment of patients with advanced classic Kaposi's sarcoma (CKS): a single-arm trial (oral etoposide in CKS). J Eur Acad Dermatol Venereol 27 (6): 789-92, 2013.
18. Brambilla L, Labianca R, Boneschi V, et al.: Mediterranean Kaposi's sarcoma in the elderly. A randomized study of oral etoposide versus vinblastine. Cancer 74 (10): 2873-8, 1994.
19. Brambilla L, Boneschi V, Fossati S, et al.: Oral etoposide for Kaposi's Mediterranean sarcoma. Dermatologica 177 (6): 365-9, 1988.
20. Brambilla L, Labianca R, Ferrucci SM, et al.: Treatment of classical Kaposi's sarcoma with gemcitabine. Dermatology 202 (2): 119-22, 2001.
21. Zustovich F, Lombardi G, Pastorelli D: Important role of gemcitabine in the treatment of classic Kaposi's sarcoma. Tumori 95 (4): 562-3, 2009.
22. Zustovich F, Ferro A, Toso S: Gemcitabine for the treatment of classic Kaposi's Sarcoma: a case series. Anticancer Res 33 (12): 5531-4, 2013.
23. Ramaswami R, Polizzotto MN, Lurain K, et al.: Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. Clin Cancer Res 28 (5): 840-850, 2022.
24. Polizzotto MN, Uldrick TS, Wyvill KM, et al.: Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol 34 (34): 4125-4131, 2016.
25. Costa da Cunha CS, Lebbe C, Rybojad M, et al.: Long-term follow-up of non-HIV Kaposi's sarcoma treated with low-dose recombinant interferon alfa-2b. Arch Dermatol 132 (3): 285-90, 1996.
26. Delyon J, Biard L, Renaud M, et al.: PD-1 blockade with pembrolizumab in classic or endemic Kaposi's sarcoma: a multicentre, single-arm, phase 2 study. Lancet Oncol 23 (4): 491-500, 2022.
27. Zer A, Icht O, Yosef L, et al.: Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). Ann Oncol 33 (7): 720-727, 2022.

Treatment of AIDS-Associated Kaposi Sarcoma

Treatment of AIDS-associated Kaposi sarcoma (KS) may result in the following:

1. The disappearance or reduction in size of specific skin lesions, thereby alleviating the discomfort associated with the chronic edema and ulcerations that often accompany multiple skin tumors seen on the lower extremities.
2. Control of symptoms associated with mucosal or visceral lesions.

No data are available, however, to show that treatment improves survival.[1] In addition to antitumor treatment, essential components of an optimal KS treatment strategy in this population include antiretroviral treatment, prophylaxis for opportunistic infections, and rapid recognition and treatment of intercurrent infections. Therefore, close collaboration between oncologists and HIV specialists is vital.

Most patients with good-risk disease, defined by the AIDS Clinical Trials Group as T0, show tumor regression with antiretroviral therapy alone.[2,3,4] Patients with poor-risk disease, defined as T1, usually require a combination of antiretroviral therapy and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion.[2,3,4]

Treatment Options for AIDS-Associated Kaposi Sarcoma

Treatment options for AIDS-associated KS include the following:

1. Local modalities.
2. Chemotherapy.
3. Biological and targeted therapy.

Local modalities

Small localized lesions of KS may be treated by electrodesiccation and curettage, cryotherapy, or by surgical excision. KS tumors are also generally very responsive to local radiation therapy, and excellent palliation has been obtained with doses at 20 Gy or slightly higher.[5,6] Radiation therapy is generally reserved to treat localized areas of the skin and oral cavity. It is used less often to control pulmonary, gastrointestinal tract, or other sites of KS lesions. Localized KS lesions have also been effectively treated with intralesional injections of vinblastine.[7] Alitretinoin 0.1% gel provided local control in a randomized, prospective, multicenter trial.[8][Level of evidence B3]

Chemotherapy

In AIDS-associated KS, the already profoundly depressed immunologic status of the patient limits the therapeutic usefulness of systemic chemotherapy. Systemic chemotherapy studies in patients with AIDS-associated KS have used doxorubicin, bleomycin, vinblastine, vincristine, etoposide, paclitaxel, and docetaxel alone or in combination.[9,10,11,12,13][Level of evidence C3] The combination of antiretroviral therapy and liposomal doxorubicin resulted in a 5-year overall survival rate of 85% in 140 patients with T1 disease.[3][Level of evidence C3]

Randomized multicenter trials showed an improvement in response rate (45%–60% vs. 20%–25%) and a more favorable toxic effects profile for pegylated liposomal doxorubicin (PLD) or liposomal daunorubicin, compared with the combination of doxorubicin, bleomycin, and vincristine or bleomycin and vincristine.[14,15,16][Level of evidence B3] During antiretroviral therapy, both PLD and paclitaxel are active single agents with response rates close to 50%.[17][Level of evidence B3]

Biological and targeted therapy

Interferon alfa

The interferon alfas have also been widely studied and show a 40% objective response rate in patients with AIDS-associated KS.[18,19] In these reports, the responses differed significantly according to the following prognostic factors:

• Extent of disease.
• Prior or coexistent opportunistic infections.
• Prior treatment with chemotherapy.
• CD4 lymphocyte counts lower than 200 cells/µL.
• Presence of circulating acid-labile interferon alfa.
• Increase in beta-2-microglobulin.

Several treatment studies have combined interferon alfa with other chemotherapeutic agents. Overall, these trials have shown no benefit with the interferon-chemotherapy combinations as compared with the single-agent activities.

Recombinant interferon alfa-2a and recombinant interferon alfa-2b were the first agents approved for the treatment of KS. Approval was based on single-agent studies performed in the 1980s before the advent of antiretroviral therapy. The early studies demonstrated improved efficacy at relatively high doses.

High-dose monotherapy is rarely used today, and instead, interferon is given in combination with other anti-HIV drugs in doses of 4 to 18 million units. Neutropenia is dose limiting, and trials of doses of 1 to 10 million units combined with less myelosuppressive antiretroviral agents are in progress. Response to interferon is slow, and the maximum effect is seen after 6 or more months. Interferon should probably not be used to treat patients with rapidly progressive, symptomatic KS.

Imatinib

Imatinib is a c-kit/platelet-derived growth factor receptor inhibitor.

Evidence (imatinib):

1. A phase II trial included 30 patients with AIDS-associated KS.[20]
   • A partial response (PR) was seen in 10 of 30 previously treated patients . Previous treatment included antiretroviral therapy and chemotherapy.

Bevacizumab

Bevacizumab is a humanized, anti–vascular endothelial growth factor monoclonal antibody.

Evidence (bevacizumab):

1. A phase II study included 16 assessable patients with KS and HIV. Patients received bevacizumab intravenously (IV) on days 1 and 8 and then every 3 weeks.[21]
   • There was a response in 5 of 16 patients. These patients had not improved after prior antiretroviral therapy and chemotherapy.[21][Level of evidence C3]

Interleukin-12

Evidence (interleukin-12):

1. A phase I and phase II trial included 24 evaluable patients. Patients received interleukin-12 subcutaneously twice weekly.[22]
   • Treatment resulted in a response rate of 71% (95% confidence interval, 48%–89%).[22][Level of evidence C3]

Pomalidomide

Pomalidomide has been approved by the U.S. Food and Drug Administration for use in AIDS-associated KS.

Evidence (pomalidomide):

1. A phase I/II study of pomalidomide included 28 patients with KS. Ten patients were HIV-positive and 18 patients were HIV-negative.[23]
   • The overall response rate was 71%, and 80% among patients without HIV. The median progression-free survival was 10 months.[23]
   • Pomalidomide was generally well tolerated. Common adverse events included neutropenia, anemia, fatigue, constipation, and rash. There were few grade 3 events (neutropenia, infection, and edema).[24]

Pomalidomide is teratogenic, prescribed through a Risk Evaluation and Mitigation Strategy (REMS) program, and it should be given with aspirin to mitigate venous thromboembolism risk.

Bortezomib

Evidence (bortezomib):

1. Bortezomib was evaluated in a small phase I dose-escalation study of 17 patients with AIDS-associated KS. Patients received bortezomib IV on days 1, 8, and 15 of 28-day cycles.[25]
   • Bortezomib was relatively well tolerated and led to a PR in 60% of all evaluable patients. Among those receiving the highest bortezomib dose, 83% of patients had a PR and 17% had stable disease.

Management of Immune Reconstitution Inflammatory Syndrome in AIDS-Associated Kaposi Sarcoma

Immune reconstitution inflammatory syndrome (IRIS) is a hyperimmune response in patients with HIV/AIDS within the first 6 months of starting antiretroviral therapy. Kaposi sarcoma (KS)-associated IRIS (KS-IRIS) is not well-defined, but is considered to be the sudden clinical worsening of previous KS ("paradoxical") or the new presentation of KS ("unmasked") in close proximity to starting or modifying antiretroviral therapy.[26]

Estimates for KS-IRIS incidence vary from 2% to 39%, with the highest risk in patients with any of the following characteristics:[26,27]

• High HIV viral loads (>10,000 copies/mL).
• CD4 lymphocyte count less than 200 cells/µL.
• Detectable plasma human herpesvirus 8 DNA.
• Pulmonary KS involvement.
• Recent steroid use.

KS-IRIS typically presents with increased swelling/tenderness of lesions, new or worsening edema, and visceral or pulmonary involvement.

Management of KS-IRIS typically includes continuing antiretroviral therapy and initiating systemic treatment, such as liposomal doxorubicin or paclitaxel, for KS. The evidence for use of chemotherapy to prevent KS-IRIS is mixed, but can be considered on an individual basis.[26] Glucocorticoids are avoided due to the risk of dramatic worsening of KS.[27,28] Thalidomide has also been used for steroid-refractory IRIS.[29]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Safai B: Kaposi's sarcoma and acquired immunodeficiency syndrome. In: DeVita VT, Hellman S, Rosenberg S, eds.: AIDS: Etiology, Diagnosis, Treatment and Prevention. 4th ed. Lippincott-Raven Publishers, 1997, pp 295-318.
2. Krown SE: Highly active antiretroviral therapy in AIDS-associated Kaposi's sarcoma: implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi's sarcoma. J Clin Oncol 22 (3): 399-402, 2004.
3. Bower M, Dalla Pria A, Coyle C, et al.: Prospective stage-stratified approach to AIDS-related Kaposi's sarcoma. J Clin Oncol 32 (5): 409-14, 2014.
4. Krell J, Stebbing J: Broader implications of a stage-guided stratified therapeutic approach for AIDS-related Kaposi's sarcoma. J Clin Oncol 32 (5): 373-5, 2014.
5. Singh NB, Lakier RH, Donde B: Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma--a prospective randomized trial. Radiother Oncol 88 (2): 211-6, 2008.
6. Tsao MN, Sinclair E, Assaad D, et al.: Radiation therapy for the treatment of skin Kaposi sarcoma. Ann Palliat Med 5 (4): 298-302, 2016.
7. Epstein JB, Lozada-Nur F, McLeod WA, et al.: Oral Kaposi's sarcoma in acquired immunodeficiency syndrome. Review of management and report of the efficacy of intralesional vinblastine. Cancer 64 (12): 2424-30, 1989.
8. Bodsworth NJ, Bloch M, Bower M, et al.: Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's sarcoma. Am J Clin Dermatol 2 (2): 77-87, 2001.
9. Evans SR, Krown SE, Testa MA, et al.: Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study. J Clin Oncol 20 (15): 3236-41, 2002.
10. Saville MW, Lietzau J, Pluda JM, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 346 (8966): 26-8, 1995.
11. Lim ST, Tupule A, Espina BM, et al.: Weekly docetaxel is safe and effective in the treatment of advanced-stage acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer 103 (2): 417-21, 2005.
12. Gill PS, Tulpule A, Espina BM, et al.: Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma. J Clin Oncol 17 (6): 1876-83, 1999.
13. Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al.: Management of AIDS-related Kaposi's sarcoma. Lancet Oncol 8 (2): 167-76, 2007.
14. Stewart S, Jablonowski H, Goebel FD, et al.: Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group. J Clin Oncol 16 (2): 683-91, 1998.
15. Northfelt DW, Dezube BJ, Thommes JA, et al.: Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol 16 (7): 2445-51, 1998.
16. Gill PS, Wernz J, Scadden DT, et al.: Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma. J Clin Oncol 14 (8): 2353-64, 1996.
17. Cianfrocca M, Lee S, Von Roenn J, et al.: Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. Cancer 116 (16): 3969-77, 2010.
18. Real FX, Oettgen HF, Krown SE: Kaposi's sarcoma and the acquired immunodeficiency syndrome: treatment with high and low doses of recombinant leukocyte A interferon. J Clin Oncol 4 (4): 544-51, 1986.
19. Groopman JE, Gottlieb MS, Goodman J, et al.: Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med 100 (5): 671-6, 1984.
20. Koon HB, Krown SE, Lee JY, et al.: Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol 32 (5): 402-8, 2014.
21. Uldrick TS, Wyvill KM, Kumar P, et al.: Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol 30 (13): 1476-83, 2012.
22. Little RF, Pluda JM, Wyvill KM, et al.: Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 107 (12): 4650-7, 2006.
23. Ramaswami R, Polizzotto MN, Lurain K, et al.: Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. Clin Cancer Res 28 (5): 840-850, 2022.
24. Polizzotto MN, Uldrick TS, Wyvill KM, et al.: Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. J Clin Oncol 34 (34): 4125-4131, 2016.
25. Reid EG, Suazo A, Lensing SY, et al.: Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma. Clin Cancer Res 26 (3): 558-565, 2020.
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Treatment of Transplant-Related Kaposi Sarcoma

Treatment Options for Transplant-Related Kaposi Sarcoma

In general, transplant-related Kaposi sarcoma is effectively managed by reduction in immunosuppression and does not require systemic treatment. Transitioning immunosuppression therapy to an mTOR inhibitor, such as sirolimus, has demonstrated efficacy in small studies and can be considered.[1]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Stallone G, Schena A, Infante B, et al.: Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 352 (13): 1317-23, 2005.

Latest Updates to This Summary (09 / 21 / 2023)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed and extensively revised.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Kaposi sarcoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
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Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Kaposi Sarcoma Treatment are:

• Minh Tam Truong, MD (Boston University Medical Center)
• Vinayak Venkataraman, MD

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Kaposi Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/kaposi-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389335]

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Last Revised: 2023-09-21