A M Di Giacomo1, P A Ascierto2, P Queirolo3, L Pilla4, R Ridolfi5, M Santinami6, A Testori7, E Simeone2, M Guidoboni5, A Maurichi6, L Orgiano3, G Spadola7, M Del Vecchio8, R Danielli1, L Calabrò1, D Annesi1, D Giannarelli9, C Maccalli10, E Fonsatti1, G Parmiani4, M Maio11. 1. Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena. 2. Medical Oncology and Innovative Therapies, Fondazione 'G. Pascale', National Cancer Institute, Naples. 3. Medical Oncology 2, IRCCS, AOU San Martino, Genoa. 4. Melanoma Unit, San Raffaele Scientific Institute, Milan. 5. Immunotherapy and Somatic Cell Therapy Unit, Scientific Institute of Romagna, Meldola. 6. Melanoma and Sarcoma Unit, National Institute for Cancer Research, Milan. 7. Dermatoncological Division, Istituto Europeo di Oncologia, Milan. 8. Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan. 9. Statistical Unit, Regina Elena National Cancer Institute, Rome. 10. Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena; Italian Network for Tumor Biotherapy (NIBIT), Siena, Italy. 11. Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena. Electronic address: mmaiocro@gmail.com.
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. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.
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. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.
Authors: Cristina Maccalli; Diana Giannarelli; Filippo Capocefalo; Lorenzo Pilla; Ester Fonsatti; Anna Maria Di Giacomo; Giorgio Parmiani; Michele Maio Journal: Oncoimmunology Date: 2015-08-12 Impact factor: 8.110
Authors: Mark Owyong; Niloufar Hosseini-Nassab; Gizem Efe; Alexander Honkala; Renske J E van den Bijgaart; Vicki Plaks; Bryan Ronain Smith Journal: Drug Resist Updat Date: 2017-10-14 Impact factor: 18.500
Authors: Yang Wang; Bin Lian; Lu Si; ZhiHong Chi; XiNan Sheng; Xuan Wang; LiLi Mao; BiXia Tang; SiMing Li; XieQiao Yan; Xue Bai; Li Zhou; ChuanLiang Cui; Jun Guo Journal: J Cancer Res Clin Oncol Date: 2021-02-21 Impact factor: 4.553