title: Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study.
abstract: The intratumoral injection of cytokines, in particular IL2, has shown promise for cutaneous melanoma patients with unresectable disease or continuous recurrence despite surgery. We recently reported that the intralesional injection of L19-IL2, an immunocytokine combining IL2 and the human monoclonal antibody fragment L19, resulted in efficient regional control of disease progression, increased time to distant metastasis and evidence of effect on circulating immune cell populations. We have also shown in preclinical models of cancer a remarkable synergistic effect of the combination of L19-IL2 with L19-TNF, a second clinical-stage immunocytokine, based on the same L19 antibody fused to TNF. Here, we describe the results of a phase II clinical trial based on the intralesional administration of L19-IL2 and L19-TNF in patients with stage IIIC and IVM1a metastatic melanoma, who were not candidate to surgery. In 20 efficacy-evaluable patients, 32 melanoma lesions exhibited complete responses upon intralesional administration of the two products, with mild side effects mainly limited to injection site reactions. Importantly, we observed complete responses in 7/13 (53.8 %) non-injected lesions (4 cutaneous, 3 lymph nodes), indicating a systemic activity of the intralesional immunostimulatory treatment. The intralesional administration of L19-IL2 and L19-TNF represents a simple and effective method for the local control of inoperable melanoma lesions, with a potential to eradicate them or make them suitable for a facile surgical removal of the residual mass.
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.forename: Roberto
authors.initials: R
authors.lastname: Patuzzo
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gallino
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Florio
authors.forename: Ornella
authors.initials: O
authors.lastname: Cutaia
authors.forename: Andrea
authors.initials: A
authors.lastname: Lazzeri
authors.forename: Carolina
authors.initials: C
authors.lastname: Fazio
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Leonardo
authors.initials: L
authors.lastname: Giovannoni
authors.forename: Giuliano
authors.initials: G
authors.lastname: Elia
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D055815:Young Adult
chemical_list: C554817:L19-IL2 immunocytokine; C558733:L19mTNFalpha protein; D011993:Recombinant Fusion Proteins