title: Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.
abstract: Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute "Fondazione G.Pascale" through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1-4). Median overall survival (OS) for all 21 patients was 13 months (range 6-26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5-50.3) vs. 8.3 months (range 7.6-9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Grimaldi
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.affiliation: Statistical Unit; Regina Elena National Cancer Institute; Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Radiotherapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Muto
authors.affiliation: Radiotherapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Falivene
authors.affiliation: Radiotherapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Borzillo
authors.affiliation: Radiotherapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Francesca Maria
authors.initials: FM
authors.lastname: Giugliano
authors.affiliation: Radiology Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sandomenico
authors.affiliation: Radiology Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Petrillo
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Curvietto
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Paone
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Palla
authors.affiliation: National Research Council; Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Caracò
authors.affiliation: Scientific Direction; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Melanoma and Sarcoma Surgery Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
authors.affiliation: Melanoma, Cancer Immunotherapy, and Innovative Therapy Unit; Istituto Nazionale Tumori Fondazione "G. Pascale"; Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
keywords: abscopal; combination; expanded access; ipilimumab; melanoma; radiotherapy
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