A cura di Alessandra Russo. Specialista in Tossicologia Medica. Messina
L’impiego di inibitori dei checkpoint immunitari è risultato associato all’insorgenza di eventi avversi immunitari.
In un articolo pubblicato sulla rivista Frontiers in Pharmacology (1) è stata focalizzata l’attenzione sui casi di epatite immuno-mediata in pazienti trattati con inibitori dei checkpoint immunitari.
Di seguito si riporta un’ampia sintesi dell’articolo con una tabella riepilogativa.
Tabella. Casi di epatite immuno-mediata osservati in pazienti trattati con inibitori dei checkpoint immunitari.
|
Farmaco |
Indicazione |
Numero pazienti |
Incidenza totale di IMH |
Incidenza di IMH di grado 3-4 |
|
Ipilimumab
|
Melanoma (2) Melanoma (3) Melanoma (4) Melanoma (5) |
151 256 57 71 |
4 (2,65%) 3 (1,17%) 8 (14,04%) 2 (2,82%) |
2 (1,32%) 1 (0,39%) 7 (12,28%) 2 (2,82%) |
|
Nivolumab
|
Melanoma (6) NSCLC avanzato (7) Melanoma (8) |
313 391 359 |
1 (0,32%) 5 (1,28%) 9 (2,51%) |
1 (0,32%) 4 (1,02%) 4 (1,11%) |
|
Cemiplimab |
NSCLC avanzato (9) Carcinoma cervicale (10) cSCC (11) |
355 300 78 |
2 (0,56%) 0 1 (1,28%) |
2 (0,56%) 4 (1,33%) 1 (1,28%) |
|
Pembrolizumab |
Melanoma (12) Melanoma (3) HCC (13) HCC (14) |
509 277 104 279 |
9 (1,77%) 5 (1,81%) 3 (2,88%) 5 (1,79%) |
7 (1,38%) 5 (1,81%) 3 (2,88%) 4 (1,43%) |
|
Atezolizumab
|
NSCLC avanzato (15) Carcinoma uroteliale (16) |
68 390 |
1 (1,47%) 36 (9,23%) |
1 (1,47%) 9 (2,31%) |
|
Avelumab |
CCRC (17) |
55 |
3 (5,45%) |
2 (3,64%) |
|
Durvalumab |
Carcinoma uroteliale (18) |
345 |
1 (0,29%) |
1 (0,29%) |
|
Nivolumab + Ipilimumab |
Melanoma (19) Melanoma (6) HCC (20) HCC (20) HCC (20) |
313 313 49 49 49 |
7 (2,23%) 1 (0,32%) 10 (20,41%) 6 (12,24%) 3 (6,12%) |
5 (1,6%) 1 (0,32%) 10 (20,41%) 5 (10,2%) 3 (6,12%) |
|
Pembrolizumab + Ipilimumab |
NSCLC metastatico (21) Melanoma (22) |
282 153 |
5 (1,77%) 15 (9,8%) |
4 (1,42%) 9 (5,88%) |
NSCLC: carcinoma polmonare non a piccole cellule; HCC: carcinoma epatocellulare; cSCC: carcinoma cutaneo a cellule squamose; CCRC: carcinoma renale a cellule chiare.
Bibliografia
- Liu Z, et al. Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives. Front Pharmacol 2023; 13: 1077468.
- Aamdal E, et al. Ipilimumab in a real-world population: A prospective phase IV trial with long-term follow-up. Int J Cancer 2022; 150: 100–111.
- Robert C, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372: 2521–2532.
- Weber J, et al. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 2009; 15: 5591–5598.
- Wolchok JD, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: A randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010; 11: 155–164.
- Wolchok JD, et al. Long-Term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol 2022; 40: 127–137.
- Paz-Ares LG, et al. First-line nivolumab plus ipilimumab in advanced NSCLC: 4-Year outcomes from the randomized, open-label, phase 3 CheckMate 227 Part 1 trial. J Thorac Oncol 2022; 17: 289–308.
- Tawbi HA, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 2022; 386: 24–34.
- Sezer A, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: A multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet 2021; 397: 592–604.
- Tewari KS, et al. Survival with cemiplimab in recurrent cervical cancer. N Engl J Med 2022; 386: 544–555.
- Migden MR, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: Results from an open-label, phase 2, single-arm trial. Lancet Oncol 2020; 21: 294–305.
- Eggermont AMM, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 2018; 378: 1789–1801.
- Zhu AX, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol 2018; 19: 940–952.
- Finn RS, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020; 382: 1894–1905.
- Cho BC, et al. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol 2022; 23: 781–792.
- Bellmunt J, et al. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2021; 22: 525–537.
- Choueiri TK, et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN renal 100): An open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol 2018; 19: 451–460.
- Powles T, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2020; 21: 1574–1588.
- Hodi FS, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19: 1480–1492.
- Yau T, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The CheckMate 040 randomized clinical trial. JAMA Oncol 2020; 6:
- Boyer M, et al. Pembrolizumab plus ipilimumab or placebo for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50%: Randomized, double-blind phase III KEYNOTE-598 study. J Clin Oncol 2021; 39: 2327–2338.
- Long GV, et al. Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): An open-label, phase 1b trial. Lancet Oncol 2017; 18: 1202–1210.