Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study

A. M. Di Giacomo, P. A. Ascierto, P. Queirolo, L. Pilla, R. Ridolfi, M. Santinami, A. Testori, E. Simeone, M. Guidoboni, A. Maurichi, L. Orgiano, G. Spadola, M. Del Vecchio, R. Danielli, L. Calabrò, D. Annesi, D. Giannarelli, Cristina Maccalli, E. Fonsatti, G. Parmiani & 1 others Michele Maio

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3+CD4+ICOS+CD45RO+ or CD45RA+ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Results: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. Conclusions: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab.

Original languageEnglish
Pages (from-to)798-803
Number of pages6
JournalAnnals of Oncology
Volume26
Issue number4
DOIs
Publication statusPublished - 1 Apr 2015
Externally publishedYes

Fingerprint

fotemustine
Biological Therapy
Melanoma
Neoplasms
Neoplasm Metastasis
Brain
Survival
Neutrophils
Survival Rate
Lymphocytes
Confidence Intervals
T-Lymphocytes
ipilimumab
Pruritus

Keywords

  • CTLA-4
  • Fotemustine
  • Immunotherapy
  • Ipilimumab
  • Metastatic melanoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study. / Di Giacomo, A. M.; Ascierto, P. A.; Queirolo, P.; Pilla, L.; Ridolfi, R.; Santinami, M.; Testori, A.; Simeone, E.; Guidoboni, M.; Maurichi, A.; Orgiano, L.; Spadola, G.; Del Vecchio, M.; Danielli, R.; Calabrò, L.; Annesi, D.; Giannarelli, D.; Maccalli, Cristina; Fonsatti, E.; Parmiani, G.; Maio, Michele.

In: Annals of Oncology, Vol. 26, No. 4, 01.04.2015, p. 798-803.

Research output: Contribution to journalArticle

Di Giacomo, AM, Ascierto, PA, Queirolo, P, Pilla, L, Ridolfi, R, Santinami, M, Testori, A, Simeone, E, Guidoboni, M, Maurichi, A, Orgiano, L, Spadola, G, Del Vecchio, M, Danielli, R, Calabrò, L, Annesi, D, Giannarelli, D, Maccalli, C, Fonsatti, E, Parmiani, G & Maio, M 2015, 'Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study', Annals of Oncology, vol. 26, no. 4, pp. 798-803. https://doi.org/10.1093/annonc/mdu577
Di Giacomo, A. M. ; Ascierto, P. A. ; Queirolo, P. ; Pilla, L. ; Ridolfi, R. ; Santinami, M. ; Testori, A. ; Simeone, E. ; Guidoboni, M. ; Maurichi, A. ; Orgiano, L. ; Spadola, G. ; Del Vecchio, M. ; Danielli, R. ; Calabrò, L. ; Annesi, D. ; Giannarelli, D. ; Maccalli, Cristina ; Fonsatti, E. ; Parmiani, G. ; Maio, Michele. / Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study. In: Annals of Oncology. 2015 ; Vol. 26, No. 4. pp. 798-803.
@article{bba9126707204653bc422f063d6cb501,
title = "Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study",
abstract = "Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3+CD4+ICOS+CD45RO+ or CD45RA+ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Results: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95{\%} confidence interval (CI) 7.1-18.7 months] and 28.5{\%} for the whole study population, and 12.7 months (95{\%} CI 2.7-22.7 months) and 27.8{\%} for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21{\%} of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'na{\"i}ve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. Conclusions: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab.",
keywords = "CTLA-4, Fotemustine, Immunotherapy, Ipilimumab, Metastatic melanoma",
author = "{Di Giacomo}, {A. M.} and Ascierto, {P. A.} and P. Queirolo and L. Pilla and R. Ridolfi and M. Santinami and A. Testori and E. Simeone and M. Guidoboni and A. Maurichi and L. Orgiano and G. Spadola and {Del Vecchio}, M. and R. Danielli and L. Calabr{\`o} and D. Annesi and D. Giannarelli and Cristina Maccalli and E. Fonsatti and G. Parmiani and Michele Maio",
year = "2015",
month = "4",
day = "1",
doi = "10.1093/annonc/mdu577",
language = "English",
volume = "26",
pages = "798--803",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study

AU - Di Giacomo, A. M.

AU - Ascierto, P. A.

AU - Queirolo, P.

AU - Pilla, L.

AU - Ridolfi, R.

AU - Santinami, M.

AU - Testori, A.

AU - Simeone, E.

AU - Guidoboni, M.

AU - Maurichi, A.

AU - Orgiano, L.

AU - Spadola, G.

AU - Del Vecchio, M.

AU - Danielli, R.

AU - Calabrò, L.

AU - Annesi, D.

AU - Giannarelli, D.

AU - Maccalli, Cristina

AU - Fonsatti, E.

AU - Parmiani, G.

AU - Maio, Michele

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3+CD4+ICOS+CD45RO+ or CD45RA+ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Results: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. Conclusions: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab.

AB - Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3+CD4+ICOS+CD45RO+ or CD45RA+ T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. Results: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. Conclusions: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab.

KW - CTLA-4

KW - Fotemustine

KW - Immunotherapy

KW - Ipilimumab

KW - Metastatic melanoma

UR - http://www.scopus.com/inward/record.url?scp=84926507093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926507093&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdu577

DO - 10.1093/annonc/mdu577

M3 - Article

VL - 26

SP - 798

EP - 803

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 4

ER -