Published 2017
| Version v1
Publication
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
Creators
- Queirolo P.
- Dozin B.
- Morabito A.
- Banelli B.
- Piccioli P.
- Fava C.
- Leo C.
- Carosio R.
- Laurent S.
- Fontana V.
- Ferrucci P. F.
- Martinoli C.
- Cocorocchio E.
- Battaglia A.
- Ascierto P. A.
- Capone M.
- Simeone E.
- De Galitiis F.
- Pagani E.
- Cappellini G. C. A.
- Marchetti P.
- Guida M.
- Tommasi S.
- Mandala M.
- Merelli B.
- Quaglino P.
- Fava P.
- Guidoboni M.
- Romani M.
- Spagnolo F.
- Pistillo M. P.
Contributors
Others:
- Queirolo, P.
- Dozin, B.
- Morabito, A.
- Banelli, B.
- Piccioli, P.
- Fava, C.
- Leo, C.
- Carosio, R.
- Laurent, S.
- Fontana, V.
- Ferrucci, P. F.
- Martinoli, C.
- Cocorocchio, E.
- Battaglia, A.
- Ascierto, P. A.
- Capone, M.
- Simeone, E.
- De Galitiis, F.
- Pagani, E.
- Cappellini, G. C. A.
- Marchetti, P.
- Guida, M.
- Tommasi, S.
- Mandala, M.
- Merelli, B.
- Quaglino, P.
- Fava, P.
- Guidoboni, M.
- Romani, M.
- Spagnolo, F.
- Pistillo, M. P.
Description
Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of patients with metastatic melanoma (MM). We investigated the association of CTLA-4 single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS in a cohort of 173 MM patients. Patients were genotyped for six CTLA-4 SNVs (-1661A > G, -1577G > A, -658C > T, -319C > T, +49A > G, and CT60G > A). We assessed the association between SNVs and BOR through multinomial logistic regression (MLR) and the prognostic effect of SNVs on OS through Kaplan-Meier method. Both -1577G > A and CT60G > A SNVs were found significantly associated with BOR. In particular, the proportion of responders was higher in G/G genotype while that of stable patients was higher in A/A genotype. The frequency of patients experiencing progression was similar in all genotypes. MLR evidenced a strong downward trend in the probability of responsiveness/progression, in comparison to disease stability,as a function of the allele A "dose" (0, 1, or 2) in both SNVs with reductions of about 70% (G/A vs G/G) and about 95% (A/A vs G/G). Moreover, -1577G/G and CT60G/G genotypes were associated with long-term OS, the surviving patients being at 3 years 29.8 and 30.8%, respectively, as compared to 12.9 and 14.4% of surviving patients carrying -1577G/A and CT60G/A, respectively. MM patients carrying -1577G/G or CT60G/G genotypes may benefit from IPI treatment in terms of BOR and long-term OS. These CTLA-4 SNVs may serve as potential biomarkers predictive of favorable outcome in this subset of patients.
Additional details
Identifiers
- URL
- https://hdl.handle.net/11567/1183997
- URN
- urn:oai:iris.unige.it:11567/1183997
Origin repository
- Origin repository
- UNIGE