Table 1.
Patients with melanoma with germline CDKN2A mutations that have received immunotherapy for metastatic melanoma
| ID | Sex | Age | Germline CDKN2A mutation |
p16 mutations |
P14ARF mutations |
Tumour stage* |
BRAF mut ation |
Type of therapy* |
Line of treatment |
Year when treatment started |
Previous therapies† |
Resp onse |
Grade 3–4 side effects |
Overall survival (months)‡ |
Progression-free survival (months)‡ |
| 1 | M | 43 | c.301G>T | Missense | Missense | M1a | V600E | CTLA-4 | 1 | 2014 | – | CR | No | 33+ | 33+ |
| 2 | F | 42 | c.301G>T | Missense | Missense | M1a | – | CTLA-4 | 1 | 2006 | – | CR | No | 138+ | 41 |
| 3 | M | 69 | c.337_338insGTC | Insertion | Insertion | M1d | – | CTLA-4 | 1 | 2012 | – | PR | No | 24 | 12 |
| 4 | M | 54 | c.301G>T | Missense | Missense | M1c | – | CTLA-4 | 1 | 2015 | – | SD | No | 12 | 6 |
| 5 | F | 39 | c.193G>C | – | Missense | M1b | V600E | CTLA-4 | 1 | 2013 | – | PD | No | 46 | 0 |
| 6 | M | 29 | c.225_243del119 | Frameshift | Chimaera | M1d | V600E | CTLA-4 | 2 | 2015 | BRAF | PD | Yes | 24+ | 0 |
| 7 | M | 57 | c.301G>T | Missense | Missense | M1c | V600E | CTLA-4 | 3 | 2011 | Chemo, chemo | PD | No | 2 | 0 |
| 8 | F | 69 | c.301G>T | Missense | Missense | M1c | V600E | CTLA-4 | 2 | 2015 | BRAF | PD | No | 3 | 0 |
| 9 | M | 75 | c.337_338insGTC | Insertion | Insertion | M1c | V600K | PD-1 | 2 | 2015 | BRAF | CR | Yes | 30+ | 30+ |
| 10 | M | 57 | C.79G>T | Nonsense | – | M1d | – | PD-1 | 1 | 2016 | – | PR | No | 11+ | 11+ |
| 11 | F | 62 | c.241C>T | Missense | Missense | M1c | V600E | PD-1 | 2 | 2017 | BRAF/MEK | PR | No | 4+ | 4+ |
| 12 | F | 48 | c.225_243del119 | Frameshift | Chimaera | M1c | V600E | PD-1 | 2 | 2017 | BRAF/MEK | PR | Yes | 4+ | 4+ |
| 4 | M | 54 | c.301G>T | Missense | Missense | M1c | – | PD-1 | 2 | 2015 | CTLA-4 | SD | No | 12 | 6 |
| 13 | M | 46 | c.225_243del119 | Frameshift | Chimaera | M1a | V600E | PD-1 | 2 | 2017 | BRAF/MEK | PD | No | 3+ | 0 |
| 14 | F | 59 | c.202_203GC>TT | Missense | Missense | M1c | V600E | PD-1 | 2 | 2017 | BRAF/MEK | PD | No | 3 | 0 |
| 15 | F | 57 | c.301G>T | Missense | Missense | M1c | V600E | PD-1 | 2 | 2016 | BRAF/MEK | PD | No | 3 | 0 |
| 16 | M | 55 | c.337_338insGTC | Insertion | Insertion | M1c | V600E | CTLA-4/PD-1 | 1 | 2016 | – | CR | Yes | 24+ | 24+ |
| 5 | F | 39 | c.193G>C | – | Missense | M1b | V600E | CTLA-4/PD-1 | 3 | 2017 | CTLA-4, BRAF/MEK | CR | Yes | 3+ | 3+ |
| 17 | F | 43 | c.-34G>T | Initiation | – | M1d | V600E | CTLA-4/PD-1 | 2 | 2017 | BRAF/MEK | PD | No | 1 | 0 |
| 18 | M | 33 | c.225_243del119 | Frameshift | Chimaera | M1d | – | ACT | 1 | 2005 | – | CR | No | 132+ | 132+ |
| 19 | F | 64 | c.370C>T | Missense | – | M1c | V600E | PD-1/BRAF/MEK | 1 | 2017 | – | PR | No | 4+ | 4+ |
*Tumour stage according to the eighth edition of the AJCC Cancer Staging System (M1d: patients with brain metastases).
†Anti-CTLA-4 therapies: ipilimumab or tremelimumab; Anti-PD-1 therapies: pembrolizumab, nivolumab or spartalizumab; Anti-BRAF therapies: vemurafenib, dabrafenib or encorafenib; Anti-MEK therapies: trametinib or binimetinib; ACT, Adoptive T cell transfer with interfron-alpha.
‡Overall survival and progression-free survival in months from start of treatment. The +sign indicates that the patient is still alive (for overall survival) or has ongoing response (for progression-free survival).
CR, complete response; PR, progressive disease; SD, stable disease.