FDA Approves Pomalidomide for Kaposi Sarcoma

The FDA has granted an accelerated approval to pomalidomide (Pomalyst) for patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy (HAART), or in patients with Kaposi sarcoma who are HIV-negative.

The approval is based on overall response rate (ORR) data reported in a phase 1/2 trial, known as 12-C-0047. In the open-label, single-arm study, pomalidomide induced an ORR of 71% (95% CI, 51-87) in patients with HIV-positive and HIV-negative symptomatic Kaposi sarcoma, comprising a complete response (CR) rate of 14% and a partial response (PR) rate of 57%.

“Pomalyst has shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” lead 12-C-0047 investigator Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch within the Center for Cancer Research of the National Cancer Institute, stated in a press release. “Also, it provides a therapy that is taken orally and works by a different mechanism of action than the cytotoxic chemotherapy drugs generally used to treat Kaposi sarcoma.”

The 12-C-0047 trial, which was conducted under a National Institutes of Health National Cooperative Research and Development Agreement, enrolled patients with both HIV-positive and HIV-negative symptomatic Kaposi sarcoma. Most of the accrued patients had advanced disease. The study included 28 patients, 18 of whom were HIV-positive, and 10 of whom were HIV-negative. Enrollment was prohibited for patients with symptomatic pulmonary or visceral Kaposi sarcoma, history of venous or arterial thromboembolism, or procoagulant disorders.

All patients were administered pomalidomide at a dose of 5 mg once daily for 21 days of each 28-day cycle. Thromboprophylaxis with aspirin (81 mg once daily) was administered throughout the course of treatment. Patients received treatment until unacceptable toxicity. or progressive disease. ORR was the primary end point.

The 71% ORR comprised 20 responses among the 28 patients, including 4 CRs and 16 PRs. The median time to first response was 1.8 months (range, 0.9 -7.6). Across all patients, the median duration of response was 12.1 months. Further, 10 of the 20 patients who responded remained in response at ≥12 months.

The ORR was 67% in the HIV-positive cohort, and the median duration of response was 12.5 months. In the HIV-negative cohort, the ORR was 80%, with a 10.5-month median duration of response.

The most frequently reported adverse events (AEs) were maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%). Grade 3/4 AEs included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%). Grade 3/4 laboratory abnormalities that worsened in patients from baseline included decreased absolute neutrophil count (50%), decreased phosphate (25%), elevated glucose (7%) and elevated creatine kinase (7%). AEs led to study discontinuation in 3 patients.

The label for pomalidomide includes an FDA Boxed Warning regarding the potential of embryo-fetal toxicity and venous and arterial thromboembolism, and the drug is only available through the FDA REMS program.

“Patients with Kaposi sarcoma have had few options to manage their disease for two decades,” Diane McDowell, MD, vice president, Hematology Global Medical Affairs, Bristol Myers Squibb, the manufacturer of pomalidomide stated in the press release. “We’re excited that the additional research into Pomalyst in this rare disease area has resulted in our ability to provide a much-needed oral treatment option for patients.”

According to Bristol Myers Squibb, "Kaposi sarcoma is a rare form of cancer that usually presents as skin lesions, but can also develop in several other areas of the body including the lungs, lymph nodes and digestive system. The disease occurs at a rate of about 6 cases per million people each year in the United States, and mostly affects people who are immunocompromised. This oral therapy is the first new treatment option available for those with Kaposi sarcoma in more than 20 years."

Pomalidomide was previously granted a breakthrough therapy designation and orphan drug designation in this setting. The accelerated approval for pomalidomide is contingent upon results of a confirmatory trial.

Pomalidomide is also approved for use in combination with dexamethasone for patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide (Revlimid) and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Pomalyst® (pomalidomide) for AIDS-Related and HIV-Negative Kaposi Sarcoma. May 15, 2020. https://bit.ly/2WZXahZ. May 15, 2020.