Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy

Antonio M. Grimaldi, Ester Simeone, Diana Giannarelli, Paolo Muto, Sara Falivene, Valentina Borzillo, Francesca Maria Giugliano, Fabio Sandomenico, Antonella Petrillo, Marcello Curvietto, Assunta Esposito, Miriam Paone, Marco Palla, Giuseppe Palmieri, Corrado Caracò, Gennaro Ciliberto, Nicola Mozzillo, Paolo A. Ascierto

Research output: Contribution to journalArticle

195 Citations (Scopus)

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.

Original languageEnglish
Article numbere28780
JournalOncoImmunology
Volume3
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Immunotherapy
Melanoma
Radiotherapy
Survival
ipilimumab
National Cancer Institute (U.S.)
Italy
Disease Progression
Neoplasms
Monoclonal Antibodies
Neoplasm Metastasis
Brain

Keywords

  • Abscopal
  • Combination
  • Expanded access
  • Ipilimumab
  • Melanoma
  • Radiotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. / Grimaldi, Antonio M.; Simeone, Ester; Giannarelli, Diana; Muto, Paolo; Falivene, Sara; Borzillo, Valentina; Giugliano, Francesca Maria; Sandomenico, Fabio; Petrillo, Antonella; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Palmieri, Giuseppe; Caracò, Corrado; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A.

In: OncoImmunology, Vol. 3, No. 5, e28780, 2014.

Research output: Contribution to journalArticle

Grimaldi, Antonio M. ; Simeone, Ester ; Giannarelli, Diana ; Muto, Paolo ; Falivene, Sara ; Borzillo, Valentina ; Giugliano, Francesca Maria ; Sandomenico, Fabio ; Petrillo, Antonella ; Curvietto, Marcello ; Esposito, Assunta ; Paone, Miriam ; Palla, Marco ; Palmieri, Giuseppe ; Caracò, Corrado ; Ciliberto, Gennaro ; Mozzillo, Nicola ; Ascierto, Paolo A. / Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. In: OncoImmunology. 2014 ; Vol. 3, No. 5.
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AU - Simeone, Ester

AU - Giannarelli, Diana

AU - Muto, Paolo

AU - Falivene, Sara

AU - Borzillo, Valentina

AU - Giugliano, Francesca Maria

AU - Sandomenico, Fabio

AU - Petrillo, Antonella

AU - Curvietto, Marcello

AU - Esposito, Assunta

AU - Paone, Miriam

AU - Palla, Marco

AU - Palmieri, Giuseppe

AU - Caracò, Corrado

AU - Ciliberto, Gennaro

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AU - Ascierto, Paolo A.

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