Pegylated interferon with antiretroviral therapy achieves promising results in patients with difficult-to-treat Kaposi's sarcoma

Pegylated interferon alfa-2a (PegIFN) may be an effective therapy for Kaposi's sarcoma (KS) that has not responded to antiretroviral treatment or chemotherapy, Dutch investigators report in the online edition of Clinical Infectious Diseases. Doctors in Rotterdam used PegIFN to treat ten HIV-positive people with KS that had not resolved with standard therapy. A complete or partial treatment response was observed in eight patients.

“Responses were durable until the end of follow up with a median PFS [progression free survival] of 2 years,” comment the authors. “Our study provides a strong rationale for further investigation of PegIFN in AIDS-KS.”

KS is the most common AIDS-defining cancer. First-line treatment is standard combination antiretroviral therapy and this achieves a complete response in most people.

However, cases of KS progression have been observed in the context of HIV treatment and a suppressed viral load. Moreover, many patients present with already extensive or progressing disease that requires additional chemotherapy on top of HIV treatment.

This chemotherapy can achieve good responses but carries a risk of immune reconstitution inflammatory syndrome (IRIS), drug interactions and unpleasant side-effects. “Treatment remains challenging, due to relapses, disease progression and treatment toxicity,” note the authors.

Interferon alfa is approved for the treatment of AIDS-related KS. The pegylated form of the drug (PegIFN) has superior efficacy and is less toxic. Doctors in Rotterdam therefore wanted to see if PegIFN in combination with antiretroviral therapy was an effective treatment for advanced KS that had not resolved with standard treatments.

Their study population consisted of ten people who were diagnosed with KS between 1991 and 2012. PegIFN therapy consisted of weekly subcutaneous injections with a 180 μg dose. The duration of therapy was not predefined. Instead it was based on the speed and completeness of response.

Eight of the participants were gay men and two were African women. KS was the first AIDS-defining illness in six people.

Therapy with PegIFN was provided between 2005 and 2012. All the participants were taking HIV therapy when this treatment was started. Eight people had an undetectable viral load at baseline and the two other individuals achieved viral suppression after changing their antiretroviral combination.

All the patients had stage T1 KS, indicating a poor prognosis. Seven participants had extensive cutaneous and visceral KS; two individuals had extensive cutaneous disease and ulcerative KS of the lower extremities; and the remaining patient had oral and visceral KS with lymph node involvement.

A treatment response was observed in eight participants. This included seven individuals who cleared KS and one individual who had a partial response. All these individuals maintained their response to the time of last follow-up, a median of 645 days.

Treatment with PegIFN initially achieved a partial response in another participant. However, disease progression including pulmonary KS led to the discontinuation of PegIFN treatment. Cutaneous lesions responded to a second course of therapy but the pulmonary lesions continued to progress.

The tenth patient was critically ill and died with 29 days due to progressive KS and multicentric Castleman’s disease (a KS-like illness).

All the participants experienced side-effects. However, none were serious, nor led to the discontinuation of PegIFN therapy.

“In this observational study, the administration of PegIFN for AIDS-KS resulted in a partial or complete remission of 8 of 10 patients,” comment the investigators. They acknowledge that their findings are limited by the design of the study, especially its lack of randomisation or a control arm. Nevertheless, they believe their results show PegIFN could be an effective therapy for KS and also provide a context for more research. “Future studies could identify subgroups of patients that would benefit most from PegIFN and provide information on optimal timing and duration of PegIFN,” suggest the authors.

They conclude: “Combining PegIFN with HAART could be an effective therapy in extensive or treatment refractory AIDS-KS.”