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Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial.
- Source :
-
Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2024 Sep 04; Vol. 17 (9), pp. 429-436. - Publication Year :
- 2024
-
Abstract
- Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased proinflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (NCT01327846) evaluated the neutralizing anti-IL1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab versus those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL1β blockade cooperating with CH mutations to modify the disease course. Prevention Relevance: We reveal that administering canakinumab is associated with a decrease in non-hematological malignancies among patients with clonal hematopoiesis (CH) mutations. These findings underscore canakinumab's potential in preventing cancer and provide proof of IL1β blockade collaborating with CH mutations to enhance its clinical benefits. See related Spotlight, p. 399.<br /> (©2024 American Association for Cancer Research.)
- Subjects :
- Humans
Female
Male
Incidence
Aged
Interleukin-1beta genetics
Middle Aged
Dioxygenases
DNA-Binding Proteins genetics
Aged, 80 and over
Follow-Up Studies
Mutation
Antibodies, Monoclonal, Humanized therapeutic use
Clonal Hematopoiesis genetics
Neoplasms genetics
Neoplasms drug therapy
Neoplasms epidemiology
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6215
- Volume :
- 17
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Publication Type :
- Academic Journal
- Accession number :
- 38701435
- Full Text :
- https://doi.org/10.1158/1940-6207.CAPR-23-0342