FDA Approves Pomalidomide for Patients with AIDS-Related Kaposi Sarcoma

May 15, 2020

Pomalidomide was approved for patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active antiretroviral therapy, or in patients with Kaposi sarcoma who are HIV-negative.

The FDA approved 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 only oral agent for this patient population, and the first in more than 20 years.

“[Pomalidomide] has shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch within the Center for Cancer Research of the National Cancer Institute, said 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.”

Pomalidomide was granted accelerated approval, breakthrough therapy designation, and orphan drug designation based on overall response rates observed in a phase I/II open label, single arm clinical trial (12-C-0047). 

The phase I/II study was conducted to evaluate the safety, pharmacokinetics, and efficacy of pomalidomide in patients with HIV-positive and HIV-negative symptomatic Kaposi sarcoma, the majority of which have advanced disease.

The primary endpoint of the study was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR), as assessed by investigators according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for Kaposi sarcoma.

In total, 28 patients (18 HIV-positive, 10 HIV-negative) received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity. Moreover, all HIV-positive patients continued concomitant HAART. Notably, the trial excluded patients with symptomatic pulmonary or visceral Kaposi sarcoma, history of venous or arterial thromboembolism, or procoagulant disorders. 

Additionally, patients received thromboprophylaxis with 81 mg of aspirin once daily throughout therapy. The median time to first response was 1.8 months (0.9 to 7.6). 

Of the overall cohort, the ORR was 71% (95% CI, 51-87) with 14% of patients achieving CR and 57% of patients achieving a PR, respectively. Further, the median duration of response for all patients was 12.1 months (95% CI, 7.6-16.8). In addition, 50% of patients who responded maintained a response at more than 12 months with pomalidomide. 

The most common adverse events (AEs) were decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea. 

AEs were assessed in 28 patients who received treatment with pomalidomide, including 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. 

Grade 3 or 4 AEs included maculopapular rash (3.6%) diarrhea (3.6%), and peripheral edema (3.6%). Grade 3 or 4 laboratory abnormalities (≥5%) worsening from baseline included decreased absolute neutrophil count (50%), decreased phosphate (25%), elevated glucose (7%), and elevated creatine kinase (7%). 

Permanent discontinuation due to an AE occurred in 11% (3/28) of patients who received pomalidomide. No new safety signals were identified, and safety of the agent in Kaposi sarcoma was consistent with the known safety profile of pomalidomide in approved indications. 

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

Continued approval of the agent by the FDA may be dependent on verification and description of clinical benefit in a confirmatory trial. 

The FDA indicated that patients with AIDS-related Kaposi sarcoma should continue HAART for their HIV as recommended by their physician.

Reference:

U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Pomalyst® (pomalidomide) for AIDS-Related and HIV-Negative Kaposi Sarcoma [news release]. Princeton, NJ. Published May 15, 2020. news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-bristol-myers-squib-0. Accessed May 15, 2020.