FDA Approves Pomalidomide for Treatment of Kaposi Sarcoma

The FDA granted approval to pomalidomide (Pomalyst) for the treatment of patients with acquired immunodeficiency syndromes (AIDS)–related Kaposi sarcoma who have developed resistance to highly active antiretroviral therapy (HAART), or those with Kaposi sarcoma who are human immunodeficiency virus (HIV)–negative. The agent was granted accelerated approval, Breakthrough Therapy, and Orphan Drug designations by the FDA for these indications.^1,2

“Patients with Kaposi sarcoma have had few options to manage their disease for two decades,” said Diane McDowell, MD, vice president, Hematology Global Medical Affairs, Bristol Myers Squibb, in a statement. “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.”

FDA activity around pomalidomide was based on results from the phase I/II 12-C-0047 trial (NCT01495598), which was evaluating the safety, efficacy, and pharmacokinetics of the agent in this population, mainly for patients with advanced disease.

Out of the 28 patients enrolled, the overall response rate (ORR) was 71% (95% CI, 51%-87%), which included complete responses (CRs) in 14% of patients and partial response (PRs) in 57% of patients. The median duration of response (DOR) in the overall study population was 12.1 months (95% CI, 7.6-16.8). In 50% of patients, the response observed with pomalidomide was maintained at more than 12 months.

Specifically, in the HIV-positive population (n = 18), the ORR was 67% (95% CI, 41%-87%) with a median DOR of 12.5 months (95% CI, 6.5-24.9). And in the HIV-negative population (n = 10), the ORR was 80% (95% CI, 44%-98%) with a median DOR of 10.5 months (95% CI, 3.9-24.2).

No new safety signals were detected in the study and the safety profile appeared to be consistent with prior information for pomalidomide as treatment of sarcoma. The most common adverse events (AEs) that included laboratory abnormalities occurred in over 30% of patients. The AEs included decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased alanine aminotransferase, nausea and diarrhea.

AEs in patients who received pomalidomide occurred in more than 20% of patients and included any-grade 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%). In terms of grade 3/4 AEs, these included maculopapular rash (3.6%), diarrhea (3.6%) and peripheral edema (3.6%). In addition, grade 3/4 laboratory abnormalities were seen in over 5% of patients and included worsening from baseline included decreased absolute neutrophil count (50%), decreased phosphate (25%), elevated glucose (7%) and elevated creatine kinase (7%).

Eleven percent of participants discontinued treatment due to an AE.

Individuals in the open-label, single-arm study received pomalidomide at a dose of 5 mg once daily for 21 days of each 28-day cycle. Thromboprophylaxis with aspirin was also administered at 81 mg once daily over the course of treatment in the study. Both drugs were continued until unacceptable toxicity. or progressive disease. ORR was the primary end point of the study.

In other studies, pomalidomide has shown promise as treatment of Kaposi sarcoma regardless of HIV status. Pomalidomide also has an indication in combination with dexamethasone for the treatment of patient 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 their last therapy.

References:

_{U.S. Food and Drug Administration approves Bristol Myers Squibb’s Pomalyst® (pomalidomide) for aids-related and hiv-negative Kaposi sarcoma [news release]. Princeton, New Jersey: Bristol Myers Squibb; May 15, 2020. https://bit.ly/2Arsf6x. Accessed May 15, 2020.}

_{FDA grants accelerated approval to pomalidomide for Kaposi sarcoma [news release]. FDA: May 15, 2020. https://bit.ly/2WzT6Gg. Accessed May 15, 2020.}