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. 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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 -