title: Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study.
abstract: Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4+and CD8+cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 ( P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity.
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Peer
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Margaret
authors.initials: M
authors.lastname: Bevans
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Frank
authors.initials: F
authors.lastname: Maldarelli
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Priscila H
authors.initials: PH
authors.lastname: Goncalves
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Vikram
authors.initials: V
authors.lastname: Khetani
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.affiliation: Mark N. Polizzotto, Thomas S. Uldrick, Kathleen M. Wyvill, Karen Aleman, Cody J. Peer, Frank Maldarelli, Priscila H. Goncalves, William D. Figg, Seth M. Steinberg, and Robert Yarchoan, National Cancer Institute; Margaret Bevans, National Institutes of Health; Irini Sereti, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Denise Whitby and Vickie Marshall, Frederick National Cancer Laboratory for Cancer Research, Frederick, MD; and Vikram Khetani and Jerome B. Zeldis, Celgene Corporation, Summit, NJ.
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; C467566:pomalidomide