Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma

Ester Simeone, Giusy Gentilcore, Diana Giannarelli, Antonio M. Grimaldi, Corrado Caracò, Marcello Curvietto, Assunta Esposito, Miriam Paone, Marco Palla, Ernesta Cavalcanti, Fabio Sandomenico, Antonella Petrillo, Gerardo Botti, Franco Fulciniti, Giuseppe Palmieri, Paola Queirolo, Paolo Marchetti, Virginia Ferraresi, Gaetana Rinaldi, Maria Pia Pistillo & 3 others Gennaro Ciliberto, Nicola Mozzillo, Paolo A. Ascierto

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Background: Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Patients and methods: Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Results: Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Conclusion: Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

Original languageEnglish
Pages (from-to)675-683
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume63
Issue number7
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

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Melanoma
Survival
Therapeutics
Immune System Diseases
Lymphocyte Count
Regulatory T-Lymphocytes
ipilimumab
C-Reactive Protein
Biomarkers
Clinical Trials
Physicians
Skin
Serum
Research
Neoplasms

Keywords

  • Biomarker
  • Expanded access programme
  • Immunological
  • Ipilimumab
  • Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. / Simeone, Ester; Gentilcore, Giusy; Giannarelli, Diana; Grimaldi, Antonio M.; Caracò, Corrado; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Cavalcanti, Ernesta; Sandomenico, Fabio; Petrillo, Antonella; Botti, Gerardo; Fulciniti, Franco; Palmieri, Giuseppe; Queirolo, Paola; Marchetti, Paolo; Ferraresi, Virginia; Rinaldi, Gaetana; Pistillo, Maria Pia; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A.

In: Cancer Immunology, Immunotherapy, Vol. 63, No. 7, 01.01.2014, p. 675-683.

Research output: Contribution to journalArticle

Simeone, E, Gentilcore, G, Giannarelli, D, Grimaldi, AM, Caracò, C, Curvietto, M, Esposito, A, Paone, M, Palla, M, Cavalcanti, E, Sandomenico, F, Petrillo, A, Botti, G, Fulciniti, F, Palmieri, G, Queirolo, P, Marchetti, P, Ferraresi, V, Rinaldi, G, Pistillo, MP, Ciliberto, G, Mozzillo, N & Ascierto, PA 2014, 'Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma', Cancer Immunology, Immunotherapy, vol. 63, no. 7, pp. 675-683. https://doi.org/10.1007/s00262-014-1545-8
Simeone, Ester ; Gentilcore, Giusy ; Giannarelli, Diana ; Grimaldi, Antonio M. ; Caracò, Corrado ; Curvietto, Marcello ; Esposito, Assunta ; Paone, Miriam ; Palla, Marco ; Cavalcanti, Ernesta ; Sandomenico, Fabio ; Petrillo, Antonella ; Botti, Gerardo ; Fulciniti, Franco ; Palmieri, Giuseppe ; Queirolo, Paola ; Marchetti, Paolo ; Ferraresi, Virginia ; Rinaldi, Gaetana ; Pistillo, Maria Pia ; Ciliberto, Gennaro ; Mozzillo, Nicola ; Ascierto, Paolo A. / Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. In: Cancer Immunology, Immunotherapy. 2014 ; Vol. 63, No. 7. pp. 675-683.
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AU - Simeone, Ester

AU - Gentilcore, Giusy

AU - Giannarelli, Diana

AU - Grimaldi, Antonio M.

AU - Caracò, Corrado

AU - Curvietto, Marcello

AU - Esposito, Assunta

AU - Paone, Miriam

AU - Palla, Marco

AU - Cavalcanti, Ernesta

AU - Sandomenico, Fabio

AU - Petrillo, Antonella

AU - Botti, Gerardo

AU - Fulciniti, Franco

AU - Palmieri, Giuseppe

AU - Queirolo, Paola

AU - Marchetti, Paolo

AU - Ferraresi, Virginia

AU - Rinaldi, Gaetana

AU - Pistillo, Maria Pia

AU - Ciliberto, Gennaro

AU - Mozzillo, Nicola

AU - Ascierto, Paolo A.

PY - 2014/1/1

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N2 - Background: Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Patients and methods: Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Results: Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Conclusion: Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

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