7 minutes reading time (1310 words)

Successfully Treating Kaposi Sarcoma: Robert Yarchoan, MD

Robert Yarchoan, MD.

Robert Yarchoan, MD, Chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI), recently spoke with i3 Health about the approval of pomalidomide (Pomalyst®, Celgene) for Kaposi sarcoma in patients with and without HIV. In this second installment of his interview, Dr. Yarchoan shares valuable advice with oncologists as they seek to enhance outcomes and treatment experiences for patients with Kaposi sarcoma.

What advice can you share with oncologists treating patients with Kaposi sarcoma?

Dr. Yarchoan: First of all, it is worth noting that while the incidence of HIV-associated Kaposi sarcoma has gone down with the widespread use of antiretroviral therapy, there is a misconception at this time that it is no longer a problem. Kaposi sarcoma continues to be the second most common AIDS-defining tumor in the United States; in particular, it is a continued problem in areas of the rural southeast US, which now have the highest incidence of HIV infections overall. It is also still the most common tumor overall in men in certain areas of sub-Saharan Africa. Also, since Kaposi sarcoma develops in elderly patients even without HIV infection, it is unclear what will occur as the HIV-infected population ages. We now often see Kaposi sarcoma in HIV-infected individuals who are either unaware that they are HIV infected or have not been on antiretroviral therapy. Kaposi sarcoma lesions can be difficult to identify in patients with dark skin, and physicians treating patients at risk should maintain a high index of suspicion.

Before treatment is undertaken, it is important to obtain a biopsy for pathological diagnosis. The cornerstone of treatment for HIV-associated Kaposi sarcoma (HIV-KS) is antiretroviral therapy. Limited HIV-KS can be initially treated with anti-HIV drugs alone, and this treatment can be relatively straightforward. However, patients with more extensive disease rarely respond to antiretroviral therapy, and some have an initial flare of their Kaposi sarcoma as part of an immune reconstitution inflammatory syndrome (IRIS). Patients with extensive or multiple lesions, painful disease, or visceral disease are generally best treated with specific systemic therapy: liposomal doxorubicin, paclitaxel, or pomalidomide. For patients with HIV-KS that requires systemic therapy, it is important to have a team consisting of an oncologist and a physician who has substantial experience in treating HIV and is aware of drug interactions involving HIV drugs.

For patients with transplantation-associated Kaposi sarcoma, regressions can often be achieved by switching from cyclosporine to rapamycin. A number of other agents have activity against Kaposi sarcoma, and physicians should consult the National Comprehensive Cancer Network® (NCCN) guidelines. Patients with more advanced Kaposi sarcoma or Kaposi sarcoma associated with inflammatory symptoms can be quite challenging to treat and are best managed by physicians with substantial experience in this area. Also, physicians should consider referring such patients to a clinical trial. It is important to remember that because Kaposi sarcoma is caused by a gammaherpesvirus that cannot be eradicated, it cannot be cured in the usual sense of the word, and relapses are common, especially in patients with continued immunosuppression. Thus, the goal of therapy should be long-term disease control with good quality of life.

Physicians treating patients with HIV-KS should be particularly alert for the coexistence of other diseases linked to Kaposi sarcoma–associated herpesvirus (KSHV), such as primary effusion lymphoma, multicentric Castleman disease, or KSHV inflammatory cytokine syndrome (KICS). Some factors that should raise suspicion for one of these conditions include fevers, malaise, ascites, edema, effusions, or anemia. C-reactive protein is usually elevated in these conditions and has utility as a screening test. The diagnosis of multicentric Castleman disease can be made by biopsy of an enlarged lymph node. Effusions should be tapped when feasible to look for primary effusion lymphoma.

Systemic glucocorticoids should be avoided in patients with Kaposi sarcoma (except as replacement therapy) when possible, as they can exacerbate Kaposi sarcoma. Physicians treating patients with Kaposi sarcoma should also remember that this is a recurrent multicentric disease; there is little role for surgery, except to make a diagnosis or remove an anatomically dangerous lesion, and if a biopsy is done, there is absolutely no need to do an excisional biopsy with a wide margin. It is important to remember that Kaposi sarcoma is a multicentric tumor, which means it arises de novo in multiple sites and does not metastasize in the usual sense of the word. Radiation therapy, previously commonly used in Kaposi sarcoma, is associated with long-term toxicity; with the availability of effective systemic therapy, it is generally not recommended.

Finally, physicians treating Kaposi sarcoma should be aware that patients are often highly distressed by the skin lesions and feel stigmatized. There is also still substantial prejudice against AIDS patients, and physicians need to be aware of this. Moreover, patients with HIV-associated Kaposi sarcoma often have financial difficulties, chaotic lives, and psychological comorbidity. Physicians should be empathetic: remember to treat the whole patient, not just the tumor.

About Dr. Yarchoan

Robert Yarchoan, MD, is a Senior Investigator and Chief of the HIV and AIDS Malignancy Branch at the NCI's Center for Cancer Research, and he is also Director of the Office of HIV and AIDS Malignancy in the NCI Office of the Director. Dr. Yarchoan played a crucial role in developing the first successful drugs to treat HIV infection, including zidovudine (AZT) and didanosine (ddI); in developing paclitaxel for Kaposi sarcoma; and in developing effective therapies for KSHV-associated multicentric Castleman Disease. His current research efforts focus on understanding and developing treatments for HIV-associated malignancies, particularly those caused by KSHV. Dr. Yarchoan is the recipient of the Assistant Secretary for Health Award, the US Public Health Service Outstanding Service Medal, the NCI HIV/AIDS Research Excellence Award, and the American Society for Microbiology's Abbott Award in Clinical and Diagnostic Immunology, among others. In December 2006, he was the recipient of the first National Institutes of Health (NIH) World AIDS Day Award. He is a Fellow of the American Association for the Advancement of Science (AAAS) and is a Member of the American Society for Clinical Investigation, the Association of American Physicians, and the American Academy of Microbiology.

Conflict of interest Statement

Dr. Yarchoan's research is funded in part by Cooperative Research and Development Agreements (CRADAs) between Celgene Corporation and the NCI. Dr. Yarchoan is also a co-inventor on US Patent 10,001,483, entitled "Methods for the treatment of Kaposi's sarcoma or KSHV-induced lymphoma using immunomodulatory compounds, and uses of biomarkers." The patent application for this was filed in part based on the results of NCI protocol 12-C-0047, entitled "A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals with or without HIV." It is his understanding that foreign patents have also been filed for this invention. This invention was made as a full-time employee of the US government under 45 Code of Federal Regulations Part 7. All rights, title, and interest to this patent have been or should by law be assigned to the US Department of Health and Human Services. The government conveys a portion of the royalties it receives to its employee-inventors under the Federal Technology Transfer Act of 1986 (P.L. 99-502).

For More Information

To gain more expert perspectives from Dr. Yarchoan concerning the treatment of Kaposi sarcoma using pomalidomide, read the first installment of this interview.

Clinicaltrials.gov (2020). Pomalidomide for Kaposi sarcoma in people with or without HIV. NLM identifier: NCT01495598.

Polizzotto MN, Uldrick TS, Wyvill KM, et al (2016). 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. DOI:10.1200/JCO.2016.69.3812

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health or the Department of Health and Human Services.

Image credit: Daniel Sone. Courtesy of the NCI

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