Published 2019
| Version v1
Publication
Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study
Creators
- 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.
Contributors
Others:
- 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.
Description
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.
Additional details
Identifiers
- URL
- https://hdl.handle.net/11567/1184001
- URN
- urn:oai:iris.unige.it:11567/1184001
Origin repository
- Origin repository
- UNIGE