Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

Abstract

Purpose: Kaposi sarcoma (KS) is caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). KS, which develops most frequently among people with HIV, is generally treated with chemotherapy, but these drugs have acute and cumulative toxicities. We previously described initial results of a trial of pomalidomide, an oral immunomodulatory derivative of thalidomide, in patients with KS. Here, we present results on the full cohort and survival outcomes.

Patients and methods: Participants with KS with or without HIV were treated with pomalidomide 5 mg once daily for 21 days per 28-day cycle with aspirin 81 mg daily for thromboprophylaxis. Participants with HIV received antiretroviral therapy. Response was defined by modified version of the AIDS Clinical Trial Group KS criteria. We evaluated tumor responses (including participants who had a second course), adverse events, progression-free survival (PFS), and long-term outcomes.

Results: Twenty-eight participants were enrolled. Eighteen (64%) were HIV positive and 21 (75%) had advanced (T1) disease. The overall response rate was 71%: 95% confidence interval (CI) 51%-87%. Twelve of 18 HIV-positive (67%; 95% CI, 41-87%) and 8 of 10 HIV-negative participants (80%; 95% CI, 44%-97%) had a response. Two of 4 participants who received a second course of pomalidomide had a partial response. The median PFS was 10.2 months (95% CI: 7.6-15.7 months). Grade 3 neutropenia was noted among 50% of participants. In the follow-up period, 3 participants with HIV had other KSHV-associated diseases.

Conclusions: Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

Conflict of interest statement

Conflicts of interest:

R. Ramaswami, K. Lurain, and R. Yarchoan report receiving research support from Celgene (now Bristol Myers Squibb) through a CRADA with the NCI. The authors also report receiving drugs for clinical trials from Merck, EMD-Serano, Eli Lilly, and CTI BioPharma through CRADAs with the NCI, and R. Yarchoan has received drug supply for laboratory research from Janssen Pharmaceuticals. Priscila Hermont Goncalves was affiliated with HIV and AIDS Malignancy Branch and is currently employed at Regeneron Pharmaceuticals, Inc. T. Uldrick, M. Polizzotto, Whitby D and R. Yarchoan are co-inventors on US Patent 10,001,483 entitled "Methods for the treatment of Kaposi's sarcoma or KSHV-induced lymphoma using immunomodulatory compounds and uses of biomarkers." R. Yarchoan is also a coinventor on patents on a peptide vaccine for HIV and both R.Yarchoan and K.Wyvill are coinventors on the treatment of Kaposi sarcoma with IL12. An immediate family member of R. Yarchoan is a co-inventor on patents related to internalization of target receptors, on KSHV viral IL-6, and on the use of calreticulin and calreticulin fragments to inhibit angiogenesis. All rights, title, and interest to these patents have been or should by law be assigned to the U.S. Department of Health and Human Services; the government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 99-502). No potential conflicts of interest were disclosed by the other authors.

©2021 American Association for Cancer Research.

Figures

Figure 1

Patient outcomes on study A) Progression-free survival (PFS) by HIV status, log-rank P=0.43 B) Swimmers’ plot to represent treatment response in all participants. Areas of color denote periods of treatment with pomalidomide.

Figure 1

Patient outcomes on study A) Progression-free survival (PFS) by HIV status, log-rank P=0.43 B) Swimmers’ plot to represent treatment response in all participants. Areas of color denote periods of treatment with pomalidomide.

Figure 2

Changes in selected inflammatory cytokines over time in all participants