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Papers of the Week

2022 Feb

J Immunother Cancer



Germline biomarkers predict toxicity to anti-PD1/PDL1 checkpoint therapy.


Weidhaas J, Marco N, Scheffler AW, Kalbasi A, Wilenius K, Rietdorf E, Gill J, Heilig M, Desler C, Chin RK, Kaprealian T, McCloskey S, Raldow A, Raja NP, Kesari S, Carrillo J, Drakaki A, Scholz M, Telesca D
J Immunother Cancer. 2022 Feb; 10(2).
PMID: 35115362.


There is great interest in finding ways to identify patients who will develop toxicity to cancer therapies. This has become especially pressing in the era of immune therapy, where toxicity can be long-lasting and life-altering, and primarily comes in the form of immune-related adverse effects (irAEs). Treatment with the first drugs in this class, anti-programmed death 1 (anti-PD1)/programmed death-ligand 1 (PDL1) checkpoint therapies, results in grade 2 or higher irAEs in up to 25%-30% of patients, which occur most commonly within the first 6 months of treatment and can include arthralgias, rash, pruritus, pneumonitis, diarrhea and/or colitis, hepatitis, and endocrinopathies. We tested the hypothesis that germline microRNA pathway functional variants, known to predict altered systemic stress responses to cancer therapies, would predict irAEs in patients across cancer types.