Pomalidomide Receives FDA Breakthrough Designation for Kaposi Sarcoma

Pomalidomide was granted a breakthrough designation by the FDA for use as treatment for both patients with HIV-positive Kaposi sarcoma who have had prior chemotherapy and patients with HIV-negative Kaposi sarcoma.

Jay Backstrom, MD

Pomalidomide (Pomalyst) has been granted a breakthrough designation by the FDA for use as treatment for both patients with HIV-positive Kaposi sarcoma who have had prior chemotherapy and patients with HIV-negative Kaposi sarcoma.1

According to findings from a phase I/II study (NCT01495598), which the FDA based this decision on, pomalidomide was well tolerated and demonstrated clinical activity in patients with Kaposi sarcoma, despite HIV status. Many of these patients had previously received cytotoxic chemotherapy.2

Celgene, the manufacturer of pomalidomide, stated in a press release that it plans to submit a supplemental new drug application for the immunomodulatory agent in this setting by the end of 2019.

“The encouraging news of the FDA breakthrough therapy designation for Pomalyst in Kaposi sarcoma reflects the urgency in accelerating the development of therapies to address diseases of this type,” said Jay Backstrom, MD, chief medical officer for Celgene. “We will continue to work closely with the agency to move this program forward for patients with this rare and serious cancer.”

Kaposi sarcoma is a multicentric tumor caused by Kaposi sarcoma-associated herpesvirus, and most frequently arises in patients with HIV infections. Currently, there are no FDA-approved therapies for HIV-positive patients who are refractory to or intolerant of chemotherapy.

In the study, which was performed under the Cooperative Research and Development Agreement and led by Robert Yarchoan, MD, of the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute (NCI), pomalidomide was evaluated in patients with symptomatic Kaposi sarcoma.

Investigators assessed pomalidomide at an initial dosage level of 5 mg once daily for 21 days per a 28-day cycle. Patients were permitted to de-escalate to 3 mg if the initial dose was not tolerated, as well as an 81-mg daily dose of aspirin for thromboprophylaxis. Patients with HIV infections required controlled viremia with either persistent Kaposi sarcoma, even with 3 months of antiretroviral therapy, or progressive Kaposi sarcoma despite 2 months of antiretroviral treatment.

To be eligible for enrollment, patients must have been ≥18 years old, had ≥5 measurable Kaposi sarcoma lesions with no prior therapy that would have prevented responses, an ECOG performance status ≤2, and a life expectancy of ≥6 months.

The primary endpoints of the trial were safety, tolerability, pharmacokinetics, as well as frequency of adverse events, response rates, and drug level measurements in the blood.

A total of 22 patients underwent treatment with pomalidomide; 15 (68%) patients had HIV infections, 17 (77%) had advanced (T1) disease, and 19 (86%) had prior therapy for Kaposi sarcoma excluding antiretroviral treatment.

All patients received pomalidomide at the 5-mg dose as no dose-limiting toxicities were reported.

Results showed that 16 patients responded to pomalidomide, leading to a 73% overall response rate (ORR; 95% CI, 50%-89%). The ORR was 60% (95% CI, 32%-84%) for patients with HIV infections and 100% (95% CI, 59%-100%) for those who did not have HIV infection. The median time to response was 4 weeks (range, 4-36).

Significant increases in CD4-positive and CD8-positive cells occurred in patients with and without HIV infection, as well as a transient increase in Kaposi sarcoma-associated herpesvirus viral load at week 4 (P= .05).

Regarding safety, grade 3/4 adverse events that were potentially treatment related included neutropenia, infection, and edema. There was no impairment on health-related quality of life during pomalidomide therapy and there was improved satisfaction with appearance at end of therapy (P= .03).

The company stated that it is planning additional trials for this patient population with the AIDS Malignancy Consortium in the United States and sub-Saharan Africa, the latter of which has less available treatments for those with HIV. The US multicenter study will be performed to confirm and extend the results of the NCI study.

Pomalidomide is currently approved in combination with dexamethasone for patients with multiple myeloma who have received ≥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.


  1. Celgene Corporation Announces POMALYST® Granted Breakthrough Therapy Designation from FDA for HIV-Positive and Negative Kaposi Sarcoma. Celgene. Published May 13, 2019. https://bit.ly/2VgaRGF. Accessed May 13, 2019.
  2. Polizzotto MN, Uldrick TS, Wykvill KM, et al. Pomalidomide for symptomatic kaposi's sarcoma in people with and without hiv infection: a phase i/ii study.J Clin Oncol. 2016;34(34):4125-4131. doi: 10.1200/JCO.201.