title: Intralesional treatment of stage III metastatic melanoma patients with L19-IL2 results in sustained clinical and systemic immunologic responses.
abstract: L19-IL2 is a recombinant protein comprising the cytokine IL2 fused to the single-chain monoclonal antibody L19. In previous studies, intralesional injection with IL2 has shown efficacy for the locoregional treatment of cutaneous/subcutaneous metastases in patients with advanced melanoma. The objectives of this study were to investigate whether (i) intralesional delivery of a targeted form of IL2 would yield similar results, with reduction of injection frequency and treatment duration; and (ii) systemic immune responses were induced by the local treatment. Patients with stage IIIB/IIIC melanoma and cutaneous/subcutaneous injectable metastases received weekly intratumoral injections of L19-IL2 at a maximum dose of 10 MIU/week for 4 consecutive weeks. Tumor response was evaluated 12 weeks after the first treatment. Twenty-four of 25 patients were evaluable for therapy-induced responses. A complete response (CR) by modified immune-related response criteria (irRC) of all treated metastases was achieved in 6 patients (25%), with long-lasting responses in most cases (5 patients for ≥24 months). Objective responses were documented in 53.9% of all index lesions [44.4% CR and 9.5% partial responses (by irRC)], and 36.5% of these remained stable, while 9.5% progressed. Toxicity was comparable with that of free IL2, and no serious adverse events were recorded. A significant temporary increase of peripheral regulatory T cells and natural killer cells, sustained increase of absolute CD4(+) lymphocytes, and decrease of myeloid-derived suppressor cells were observed upon treatment. Finally, we recorded encouraging data about the progression time to distant metastases and overall survival.
authors.affiliation: Authors' Affiliations: Departments of Dermatology, Center of Dermato-Oncology and benjamin.weide@med.uni-tuebingen.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Authors' Affiliations: Departments of Dermatology, Center of Dermato-Oncology and.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Eigentler
authors.affiliation: Authors' Affiliations: Departments of Dermatology, Center of Dermato-Oncology and.
authors.forename: Annette
authors.initials: A
authors.lastname: Pflugfelder
authors.affiliation: Internal Medicine II, Section for Transplantation Immunology and Immunohematology, University Medical Center, Tübingen;
authors.forename: Henning
authors.initials: H
authors.lastname: Zelba
authors.affiliation: Internal Medicine II, Section for Transplantation Immunology and Immunohematology, University Medical Center, Tübingen;
authors.forename: Alexander
authors.initials: A
authors.lastname: Martens
authors.affiliation: Internal Medicine II, Section for Transplantation Immunology and Immunohematology, University Medical Center, Tübingen;
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Philogen S.p.A., La Lizza, Siena, Italy;
authors.forename: Leonardo
authors.initials: L
authors.lastname: Giovannoni
authors.affiliation: Philogen S.p.A., La Lizza, Siena, Italy;
authors.forename: Pier Adelchi
authors.initials: PA
authors.lastname: Ruffini
authors.affiliation: Philochem AG, Otelfingen;
authors.forename: Giuliano
authors.initials: G
authors.lastname: Elia
authors.affiliation: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland; and.
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.affiliation: Department of Dermatology and Allergy, Hannover Medical School, Skin Cancer Center, Hannover, Germany;
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Department of Dermatology and Venereology, Universitätsklinik Graz, Graz, Austria.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Authors' Affiliations: Departments of Dermatology, Center of Dermato-Oncology and.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D009367:Neoplasm Staging; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C554817:L19-IL2 immunocytokine; D011993:Recombinant Fusion Proteins