title: Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial.
abstract: Lenalidomide, an oral immunomodulating agent, has shown promising activity in HIV-infected individuals with Kaposi's sarcoma (KS). This single-arm, multicenter, open-label, Gehan's two-stage phase II trial evaluated the efficacy and safety of lenalidomide in HIV-infected patients with progressive KS despite previous chemotherapy (NCT01282047, ANRS 154 Lenakap trial). The primary endpoint was the rate of partial response (PR) or complete response (CR) at week 24, evaluated by both the study investigators and the patients using the Physical Global Assessment (PGA). AIDS Clinical Trials Group (ACTG) criteria for KS treatment evaluation were used as a secondary endpoint. The data and safety monitoring board recommended that enrollments be halted on April 24, 2013, because of lack of responses. We enrolled 12 antiretroviral-treated HIV-infected men with progressive KS despite previous chemotherapy. Their HIV plasma viral load was <50 copies/ml and their median CD4 cell count 444/mm3. One patient stopped taking lenalidomide because of hives at week 1 and a second patient died at week 7. The remaining 10 patients were assessable at week 24, when none had PGA-defined CR or PR and one had ACTG-defined PR. There were no additional PGA responses at week 48, but an additional three patients had ACTG responses, for a total of four patients with ACTG PR at week 48 (40%; 95% confidence interval: 12.2-73.8). Fourteen grade 3-4 adverse events were considered at least possibly related to lenalidomide during a total of 101 cycles. Lenalidomide was well tolerated in antiretroviral experienced patients with progressive KS previously treated with chemotherapy. The ACTG-defined response rate at week 48 was 40%, while it was 0% using PGA criteria.
authors.affiliation: 1 Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière , Service de Maladies Infectieuses et Tropicales, Paris, France .|2 Sorbonne Universités , UPMC Paris Univ 06, Paris, France .|3 INSERM UMR-S996 , Clamart, France .
authors.forename: Valérie
authors.initials: V
authors.lastname: Pourcher
authors.affiliation: 3 INSERM UMR-S996 , Clamart, France .|4 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard , Département de Pharmaco-Toxicologie Clinique, Paris, France .
authors.forename: Aude
authors.initials: A
authors.lastname: Desnoyer
authors.affiliation: 5 INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMR 1136), Sorbonne Universités , UPMC Univ Paris 06, Paris, France .
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.affiliation: 6 Assistance Publique Hôpitaux de Paris, Hôpital Saint Louis , Service de Dermatologie, Paris, France .|7 INSERM U976, CIC et Dermatologie, Univ Paris Diderot , Paris, France .
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbe
authors.affiliation: 5 INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMR 1136), Sorbonne Universités , UPMC Univ Paris 06, Paris, France .
authors.forename: Angélique
authors.initials: A
authors.lastname: Curjol
authors.affiliation: 5 INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMR 1136), Sorbonne Universités , UPMC Univ Paris 06, Paris, France .|8 Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière , Laboratoire de Virologie, Paris, France .
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: 9 ANRS (France REcherche Nord&Sud Sida-hiv Hépatites), Clinical and Therapeutic Research on HIV/AIDS Office , Paris, France .
authors.forename: Fanny
authors.initials: F
authors.lastname: Cardon
authors.affiliation: 10 ANRS (France REcherche Nord&Sud Sida-hiv Hépatites), Clinical Research Safety Office , Paris, France .
authors.forename: Séverine
authors.initials: S
authors.lastname: Gibowski
authors.affiliation: 11 Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin , Service des Maladies Infectieuses, Paris, France .
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: 12 CHU Angers , Service de Maladies Infectieuses et Tropicales, Angers, France .
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Chennebault
authors.affiliation: 13 APHM Sainte-Marguerite , Service d'Immunohématologie Clinique, Marseille, France .|14 INSERM U912 (SESSTIM), Université Aix Marseille , Marseille, France .
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.affiliation: 4 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard , Département de Pharmaco-Toxicologie Clinique, Paris, France .|15 INSERM, IAME UMR 1137, Université Paris Diderot , Paris, France .
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: 3 INSERM UMR-S996 , Clamart, France .|16 Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère , Service de Médecine Interne et Immunologie Clinique, Clamart, France .
authors.forename: François
authors.initials: F
authors.lastname: Boué
authors.affiliation: 5 INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMR 1136), Sorbonne Universités , UPMC Univ Paris 06, Paris, France .
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide
keywords: HIV; efficacy; kaposi sarcoma; lenalidomide