Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 97-107 |
| Number of pages | 11 |
| Journal | Cancer Immunol. Immunother. |
| Volume | 68 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2019 |
Keywords
- Adverse events
- Best response
- Ipilimumab
- Overall survival
- Soluble CTLA-4
- aminotransferase
- amylase
- B Raf kinase inhibitor
- biological marker
- cytotoxic T lymphocyte antigen 4
- gilvetmab
- ipilimumab
- melanoma antigen 3
- mitogen activated protein kinase kinase inhibitor
- recombinant interferon
- recombinant interleukin 2
- triacylglycerol lipase
- immunological antineoplastic agent
- tumor marker
- adult
- aged
- Article
- cancer immunotherapy
- cancer prognosis
- clinical feature
- correlation analysis
- diarrhea
- enzyme linked immunosorbent assay
- female
- hepatitis
- human
- hypophysitis
- hypothyroidism
- Italy
- Kaplan Meier method
- liver disease
- logistic regression analysis
- major clinical study
- male
- metastatic melanoma
- mortality rate
- nausea and vomiting
- overall survival
- pancreas disease
- predictive value
- priority journal
- proportional hazards model
- pruritus
- rash
- side effect
- thyroiditis
- treatment response
- blood
- melanoma
- metabolism
- metastasis
- middle aged
- pathology
- solubility
- very elderly
- young adult
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents, Immunological
- Biomarkers, Tumor
- CTLA-4 Antigen
- Female
- Humans
- Kaplan-Meier Estimate
- Male
- Melanoma
- Middle Aged
- Neoplasm Metastasis
- Predictive Value of Tests
- Solubility
- Young Adult
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Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study : Cancer Immunology, Immunotherapy. / Pistillo, M.P.; Fontana, V.; Morabito, A.; Dozin, B.; Laurent, S.; Carosio, R.; Banelli, B.; Ferrero, F.; Spano, L.; Tanda, E.; Ferrucci, P.F.; Martinoli, C.; Cocorocchio, E.; Guida, M.; Tommasi, S.; De Galitiis, F.; Pagani, E.; Antonini Cappellini, G.C.; Marchetti, P.; Quaglino, P.; Fava, P.; Osella-Abate, S.; Ascierto, P.A.; Capone, M.; Simeone, E.; Romani, M.; Spagnolo, F.; Queirolo, P.; (IMI), On behalf of the Italian Melanoma Intergroup.
In: Cancer Immunol. Immunother., Vol. 68, No. 1, 2019, p. 97-107.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study
T2 - Cancer Immunology, Immunotherapy
AU - Pistillo, M.P.
AU - Fontana, V.
AU - Morabito, A.
AU - Dozin, B.
AU - Laurent, S.
AU - Carosio, R.
AU - Banelli, B.
AU - Ferrero, F.
AU - Spano, L.
AU - Tanda, E.
AU - Ferrucci, P.F.
AU - Martinoli, C.
AU - Cocorocchio, E.
AU - Guida, M.
AU - Tommasi, S.
AU - De Galitiis, F.
AU - Pagani, E.
AU - Antonini Cappellini, G.C.
AU - Marchetti, P.
AU - Quaglino, P.
AU - Fava, P.
AU - Osella-Abate, S.
AU - Ascierto, P.A.
AU - Capone, M.
AU - Simeone, E.
AU - Romani, M.
AU - Spagnolo, F.
AU - Queirolo, P.
AU - (IMI), On behalf of the Italian Melanoma Intergroup
N1 - Cited By :6 Export Date: 28 February 2020 CODEN: CIIMD Correspondence Address: Pistillo, M.P.; Unit of Tumor Epigenetics, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, Italy; email: mariapia.pistillo@hsanmartino.it Chemicals/CAS: aminotransferase, 9031-66-7; amylase, 9000-90-2, 9000-92-4, 9001-19-8; gilvetmab, 1808081-43-7; ipilimumab, 477202-00-9; recombinant interleukin 2, 110942-02-4; triacylglycerol lipase, 9001-62-1; Antineoplastic Agents, Immunological; Biomarkers, Tumor; CTLA-4 Antigen; Ipilimumab Funding text 1: Acknowledgements The authors would like to thank the patients and investigators who participated in the Italian Expanded Access Program (EAP). This work was supported by the Italian Melanoma Intergroup (IMI). The authors also thank the blood donors and staff of all centers, in particular the Transfusion Center of the IRCCS Ospedale Policlinico San Martino, Genoa, Italy, and the research nurse P. Peirano for collection of blood samples from melanoma patients. Funding text 2: Funding This work was supported by grants from the Italian Ministry of Health (5 × 1000 funds 2013 and 2014 to Pistillo), Italy. This work was supported by the Italian Melanoma Intergroup (IMI). The Expanded Access Program (EAP) was sponsored by Bristol-Myers Squibb. References: Hodi, F.S., O’Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., Improved survival with ipilimumab in patients with metastatic melanoma (2010) N Engl J Med, 363, pp. 711-723; Robert, C., Thomas, L., Bondarenko, I., O’Day, S., Weber, J., Garbe, C., Ipilimumab plus dacarbazine for previously untreated metastatic melanoma (2011) N Engl J Med, 364, pp. 2517-2526; Schadendorf, D., Hodi, F.S., Robert, C., Weber, J.S., Margolin, K., Hamid, O., Pooled analysis of long-term survival data from Phase II and Phase III trials of Ipilimumab in unresectable or metastatic melanoma (2015) J Clin Oncol, 33, pp. 1889-1894; Peggs, K.S., Quezada, S.A., Korman, A.J., Allison, J.P., Principles and use of anti-CTLA-4 antibody in human cancer immunotherapy (2006) Curr Opin Immunol, 18, pp. 206-231; Tarhini, A.A., Edington, H., Butterfield, L.H., Lin, Y., Shuai, Y., Tawbi, H., Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab (2014) PLoS One, 9; Brunner, M.C., Chambers, C.A., Chan, F.K., Hanke, J., Winoto, A., Allison, J.P., CTLA-4-mediated inhibition of early events of T cell proliferation (1999) J Immunol, 162, pp. 5813-5820; Walker, L.S., Sansom, D.M., The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses (2011) Nat Rev Immunol, 11, pp. 852-863; Walker, S.K., Sansom, D.M., Confusing signals: recent progress in CTLA-4 biology (2015) Trends Immunol, 36, pp. 63-70; Oaks, M.K., Hallett, K.M., Cutting edge: a soluble form of CTLA-4 in patients with autoimmune thyroid disease (2000) J Immunol, 164, pp. 5015-5018; Magistrelli, G., Jeannin, P., Herbault, N., Benoit De Coignac, A., Gauchat, J.F., A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells (1999) Eur J Immunol, 29, pp. 3596-3602; Simone, R., Pesce, G., Antola, P., Rumbullaku, M., Bagnasco, M., Bizzaro, N., Saverino, D., The soluble form of CTLA-4 from serum of patients with autoimmune diseases regulates T-cell responses (2014) Biomed Res Int, 2014, p. 215763; Simone, R., Tenca, C., Fais, F., Luciani, M., De Rossi, G., Pesce, G., A soluble form of CTLA-4 is present in paediatric patients with acute lymphoblastic leukaemia and correlates with CD1d + expression (2012) PLoS One, 7; Erfani, N., Razmkhah, M., Ghaderi, A., Circulating soluble CTLA4 (sCTLA4) is elevated in patients with breast cancer (2010) Cancer Invest, 28, pp. 828-832; Liu, Q., Hu, P., Deng, G., Zhang, J., Liang, N., Xie, J., Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant tumors after therapy (2017) Onco Targets Ther, 10, pp. 2147-2154; Ward, F.J., Dahal, L.N., Wijesekera, S.K., Abdul-Jawad, S.K., Kaewarpai, T., Xu, H., The soluble isoform of CTLA-4 as a regulator of T-cell responses (2013) Eur J Immunol, 43, pp. 1274-1285; Rydén, A., Bolmeson, C., Jonson, C.O., Cilio, C.M., Faresjö, M., Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children (2012) Diabetes Metab Res Rev, 28, pp. 84-96; Sato, S., Fujimoto, M., Hasegawa, M., Komura, K., Yanaba, K., Hayakawa, I., Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis (2004) Rheumatology, 43, pp. 1261-1266; Zaragoza, J., Caille, A., Beneton, N., Bens, G., Christiann, F., Maillard, H., Machet, L., High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma (2016) Br J Dermatol, 174, pp. 146-151; Seremet, T., Koch, A., Jansen, Y., Schreuer, M., Wilgenhof, S., Del Marmol, V.J., Molecular and epigenetic features of melanomas and tumor immune microenvironment linked to durable remission to ipilimumab-based immunotherapy in metastatic patients (2016) J Transl Med, 14 (1), p. 232; Queirolo, P., Dozin, B., Morabito, A., Banelli, B., Piccioli, P., Fava, C., Association of CTLA-4 gene variants with response to therapy and long-term survival in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study (2017) Front Immunol, 8, p. 386; Queirolo, P., Dozin, B., Morabito, A., Banelli, B., Carosio, R., Fontana, V., CTLA-4 gene variant—1661A > G may predict the onset of endocrine adverse events in metastatic melanoma patients treated with ipilimumab (2018) Eur J Cancer, 97, pp. 59-61; Ascierto, P.A., Simeone, E., Sileni, V.C., Pigozzo, J., Maio, M., Altomonte, M., Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access program cohort (2014) J Transl Med, 12, p. 116; Wolchok, J.D., Hoos, A., O’Day, S., Weber, J.S., Hamid, O., Lebbé, C., Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria (2009) Clin Cancer Res, 15, pp. 7412-7420; (2006) Common Terminology Criteria for Adverse Events V3.0 (CTCAE)., , http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf, Accessed 30 Dec 2015; Ferrucci, P.F., Ascierto, P.A., Pigozzo, J., Del Vecchio, M., Maio, M., Antonini Cappellini, G.C., Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab (2016) Ann Oncol, 27, pp. 732-738; Proctor, M.J., McMillan, D.C., Morrison, D.S., Fletcher, C.D., Horgan, P.G., Clarke, S.J., A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer (2012) Br J Cancer, 107, pp. 695-699; Kleinbaum, D.G., Klein, M., (2010) Logistic regression, , 3, Springer, New York; Kleinbaum, D.G., Klein, M., (2005) Survival analysis, , 2, Springer, New York; Ueda, H., Howson, J.M., Esposito, L., Heward, J., Snook, H., Chamberlain, G., Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease (2003) Nature, 423, pp. 506-511; Leung, A.M., Lee, A.F., Ozao-Choy, J., Ramos, R.I., Hamid, O., O’Day, S.J., Clinical benefit from ipilimumab therapy in melanoma patients may be associated with serum CTLA4 levels (2014) Front Oncol, 4, p. 110; Masuda, A., Arai, K., Nishihara, D., Mizuno, T., Yuki, H., Kambara, T., Clinical significance of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (2014) Biomed Res Int, 2014, p. 396064; Kucukhuseyin, O., Turan, S., Yanar, K., Arikan, S., Duzkoylu, Y., Aydin, S., Individual and combined effects of CTLA4-cd28 variants and oxidant-antioxidant status on the development of colorectal cancer (2015) Anticancer Res, 35, pp. 5391-5400; Laurent, S., Queirolo, P., Boero, S., Salvi, S., Piccioli, P., Boccardo, S., The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-α production (2013) J Transl Med, 11, p. 108; Weber, J.S., Kähler, K.C., Hauschild, A., Management of immune-related adverse events and kinetics of response with ipilimumab (2012) J Clin Oncol, 30, pp. 2691-2697; Chen, Z., Zhou, F., Huang, S., Jiang, T., Chen, L., Ge, L., Xia, B., Association of cytotoxic T lymphocyte associated antigen-4 gene (rs60872763) polymorphism with Crohn’s disease and high levels of serum sCTLA-4 in Crohn’s disease (2011) J Gastroenterol Hepatol, 26, pp. 924-930; Jiang, T., Ge, L.Q., Chen, Z.T., Li, C., Zhou, F., Luo, Y., Xia, B., Effect of cytotoxic T lymphocyte-associated molecule 4 1661 gene polymorphism on its expression and transcription in ulcerative colitis (2010) J Dig Dis, 11, pp. 369-375; Cao, J., Zhang, L., Huang, S., Chen, P., Zou, L., Chen, H., Aberrant production of soluble co-stimulatory molecules CTLA-4 and CD28 in patients with chronic hepatitis B (2011) Microb Pathog, 51, pp. 262-267; Umemura, T., Ota, M., Hamano, H., Katsuyama, Y., Muraki, T., Arakura, N., Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients (2008) Am J Gastroenterol, 103, pp. 588-594; Kelderman, S., Heemskerk, B., van Tinteren, H., van den Brom, R.R., Hospers, G.A., van den Eertwegh, A.J., Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma (2014) Cancer Immunol Immunother, 63, pp. 449-458; Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D.R., IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade (2017) J Clin Invest, 127, pp. 2930-2940; Tumeh, P.C., Harview, C.L., Yearley, J.H., Shintaku, I.P., Taylor, E.J., Robert, L., PD-1 blockade induces responses by inhibiting adaptive immune resistance (2014) Nature, 515, pp. 568-571; Weide, B., Martens, A., Hassel, J.C., Berking, C., Postow, M.A., Bisschop, K., Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab (2016) Clin Cancer Res, 22, pp. 5487-5496; Roncella, S., Laurent, S., Fontana, V., Ferro, P., Franceschini, M.C., Salvi, S., CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor (2016) Cancer Immunol Immunother, 65, pp. 909-917; Salvi, S., Fontana, V., Boccardo, S., Merlo, D.F., Margallo, E., Laurent, S., Morabito, A., Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer (2012) Cancer Immunol Immunother, 61, pp. 1463-1472; Hu, P., Liu, Q., Deng, G., Zhang, J., Liang, N., Xie, J., Zhang, J., The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers: a systematic review and meta-analysis (2017) Sci Rep, 7, p. 42913
PY - 2019
Y1 - 2019
N2 - CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan–Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03–1.88) and 89% (OR = 0.11; 95%CL = 0.02–0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02–19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39–0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
AB - CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan–Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03–1.88) and 89% (OR = 0.11; 95%CL = 0.02–0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02–19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39–0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
KW - Adverse events
KW - Best response
KW - Ipilimumab
KW - Overall survival
KW - Soluble CTLA-4
KW - aminotransferase
KW - amylase
KW - B Raf kinase inhibitor
KW - biological marker
KW - cytotoxic T lymphocyte antigen 4
KW - gilvetmab
KW - ipilimumab
KW - melanoma antigen 3
KW - mitogen activated protein kinase kinase inhibitor
KW - recombinant interferon
KW - recombinant interleukin 2
KW - triacylglycerol lipase
KW - immunological antineoplastic agent
KW - tumor marker
KW - adult
KW - aged
KW - Article
KW - cancer immunotherapy
KW - cancer prognosis
KW - clinical feature
KW - correlation analysis
KW - diarrhea
KW - enzyme linked immunosorbent assay
KW - female
KW - hepatitis
KW - human
KW - hypophysitis
KW - hypothyroidism
KW - Italy
KW - Kaplan Meier method
KW - liver disease
KW - logistic regression analysis
KW - major clinical study
KW - male
KW - metastatic melanoma
KW - mortality rate
KW - nausea and vomiting
KW - overall survival
KW - pancreas disease
KW - predictive value
KW - priority journal
KW - proportional hazards model
KW - pruritus
KW - rash
KW - side effect
KW - thyroiditis
KW - treatment response
KW - blood
KW - melanoma
KW - metabolism
KW - metastasis
KW - middle aged
KW - pathology
KW - solubility
KW - very elderly
KW - young adult
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Agents, Immunological
KW - Biomarkers, Tumor
KW - CTLA-4 Antigen
KW - Female
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Melanoma
KW - Middle Aged
KW - Neoplasm Metastasis
KW - Predictive Value of Tests
KW - Solubility
KW - Young Adult
U2 - 10.1007/s00262-018-2258-1
DO - 10.1007/s00262-018-2258-1
M3 - Article
VL - 68
SP - 97
EP - 107
JO - Cancer Immunol. Immunother.
JF - Cancer Immunol. Immunother.
SN - 0340-7004
IS - 1
ER -