Biomarker-Driven Personalized Immunoprevention: Toward More Efficient Clinical Trials?

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Clonal hematopoiesis (CH) is associated with increased inflammation and cancer risk.
• Interleukin-1β (IL-1β) is a key inflammatory cytokine implicated in cancer development.
• The CANTOS trial evaluated canakinumab, an anti-IL-1β monoclonal antibody, for cardiovascular risk reduction.

Purpose of the Study:

• To investigate the association between clonal hematopoiesis mutations and cancer risk reduction with canakinumab treatment.
• To explore the potential of targeting IL-1β for personalized cancer chemoprevention in individuals with CH.

Main Methods:

• Secondary analysis of patient specimens from the CANTOS randomized controlled trial.
• Genotyping of peripheral blood DNA to identify clonal hematopoiesis mutations, with a focus on TET2.
• Assessment of cancer incidence in relation to canakinumab treatment and presence of CH mutations.

Main Results:

• Patients with clonal hematopoiesis mutations, particularly TET2 mutations, showed a significant decrease in cancer risk when treated with canakinumab.
• The presence of CH mutations predicted a beneficial response to anti-IL-1β therapy in terms of cancer risk reduction.
• Although numbers were small, the findings suggest a potential biomarker for canakinumab efficacy in cancer prevention.

Conclusions:

• Clonal hematopoiesis mutations, especially in TET2, may identify patients who benefit from canakinumab for cancer risk reduction.
• These findings support the development of personalized chemoprevention strategies based on genetic profiles.
• Personalized approaches could enhance the design and feasibility of future cancer prevention trials.