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Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy

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Abstract

Current systemic treatments for metastatic uveal melanoma (UM) have not improved overall survival (OS). The fully human anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, ipilimumab, improved OS of patients with advanced cutaneous melanoma in a phase 3 trial; however, UM patients were excluded. The aim of this subanalysis, performed by the ipilimumab-ocular melanoma expanded access program (I-OMEAP) study group, was to assess the activity and safety of ipilimumab in patients with UM in a setting similar to daily clinical practice. Patients participating in a multicenter expanded access program (EAP) received induction treatment with ipilimumab 10 mg/kg. Maintenance doses were administered in patients who experienced clinical benefit or at physicians’ discretion. Tumor assessment was evaluated per modified World Health Organization criteria at baseline, Week 12, Week 24, and Week 36. Adverse events (AEs) and immune-related AEs (irAEs) were collected according to Common Terminology Criteria for Adverse Events version 3.0. Thirteen pretreated patients with metastatic UM were treated at 6 European institutions. All patients received at least one dose of ipilimumab. Overall, no objective responses were observed; however, two patients had stable disease (SD), with a third patient achieving SD after initial progressive disease. Median OS as of July 1, 2011, was 36 weeks (range 2–172+ weeks). No grade 3/4 AEs of non-immune origin were reported. Three patients (23%) experienced grade 3 irAEs (1 thrombocytopenia, 1 diarrhea, and 1 alanine/aspartate aminotransferase elevation) that resolved with steroid therapy. The results indicate UM is a potential indication for ipilimumab treatment that should be further investigated in clinical trials.

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Acknowledgments

The expanded access program was sponsored by Bristol-Myers Squibb. Editorial assistance was provided by StemScientific, funded by Bristol-Myers Squibb. The authors thank Dr Giorgio Frosini and Dr Mario Marini from the Gastroenterology Unit of the University Hospital of Siena for providing the colonoscopic pictures. They also thank the nurses (Angela Iacovelli, Sergio Speranza, Massimo Resti, and Marilena Piccinelli) and data managers (Giovanni Amato and Eliana Pittiglio) at the Medical Oncology and Immunotherapy Unit of the University Hospital of Siena for their contribution to the data collection.

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Authors and Affiliations

  1. Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Istituto Toscano Tumori, Strada delle Scotte, 53100, Siena, Italy

    Riccardo Danielli, Luana Calabrò, Anna Maria Di Giacomo, Maresa Altomonte & Michele Maio

  2. Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST), Meldola-Forlì, Italy

    Ruggero Ridolfi & Laura Ridolfi

  3. Istituto Oncologico Veneto, Padova, Italy

    Vanna Chiarion-Sileni & Costanza De Rossi

  4. National Institute for Cancer Research, Genoa, Italy

    Paola Queirolo & Monica Boitano

  5. European Institute of Oncology, Milan, Italy

    Alessandro Testori & Pier Francesco Ferrucci

  6. Newcastle University, Newcastle upon Tyne, UK

    Ruth Plummer

  7. Pathology, University Hospital of Siena, Istituto Toscano Tumori, Strada delle Scotte, 53100, Siena, Italy

    Clelia Miracco

  8. Ophthalmology, University Hospital of Siena, Istituto Toscano Tumori, Strada delle Scotte, 53100, Siena, Italy

    Angelo Balestrazzi

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  1. Riccardo Danielli
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  10. Anna Maria Di Giacomo
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  11. Pier Francesco Ferrucci
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  15. Angelo Balestrazzi
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  16. Michele Maio
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Corresponding author

Correspondence to Michele Maio.

Additional information

This study was conducted for the ipilimumab-ocular melanoma expanded access program (I-OMEAP) study group.

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Danielli, R., Ridolfi, R., Chiarion-Sileni, V. et al. Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother 61, 41–48 (2012). https://doi.org/10.1007/s00262-011-1089-0

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