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. ParmianiMichele Maio

Research output: Contribution to journalArticle

69 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

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

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, C., Fonsatti, E., ... 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, 26(4), 798-803. https://doi.org/10.1093/annonc/mdu577