Chive-Impact: Establishing the Clonal Hematopoiesis and Inflammation in the Vasculature (CHIVE) Registry and Biorepository in Underserved Areas

Introduction:

Clonal hematopoiesis (CH) is a prevalent age-related phenomenon characterized by somatic mutations in hematopoietic stem cells and associated with increased risks of hematologic malignancies and cardiovascular diseases. Most CH is benign, but determining its high-risk features is an important objective. The Clonal Hematopoiesis and Inflammation in Vasculature (CHIVE) registry and biorepository aims to prospectively study CH with the collection of serial samples to determine best how CH leads to disease. (Shannon ML et al. Blood Advances, 2024).

In 2021, the Leukemia & Lymphoma Society launched its IMPACT (Influential Medicine Providing Access to Clinical Trials) grant program, with Vanderbilt among its first recipients. The program provides funding to major cancer centers, in partnership with local community oncology practices, to help increase the participation of patients who are traditionally underrepresented in clinical trials, including those who are rural, minority, and/or economically disadvantaged. As the Mississippi Delta region has some of the highest rates of cardiovascular disease and cancer in the US, and as CHIVE is less accessible to patients in rural or underserved areas, we aimed to bring CHIVE to the Mississippi Delta region to improve understanding of the impact of health disparities on CH. Here, we describe the initial results of our CHIVE-IMPACT cohort.

Methods:

CHIVE-IMPACT leverages a collaboration between academic hub Vanderbilt-Ingram Cancer Center (VICC) and community partners Baptist Memorial Healthcare Corporation (BMHCC), which has community practices throughout the Mississippi Delta region. We screened adult oncology patients seen in BMHCC community cancer clinics and recruited to CHIVE-IMPACT any adult patient who did not have hematologic malignancy. Annotated genetic and clinical data from all consented participants is collected and stored in a registry paired with the CHIVE centralized biorepository. We used an affordable (~US $8 per sample), validated, custom oligonucleotide gene capture panel covering 95% of all CH gene mutations to perform targeted sequencing of prospective participants. (Mack T et al. The Journal of Molecular Diagnostics, 2024).

Results:

Between December 2022 and January 2024, 38 patients were enrolled and underwent sequencing, and CHIP mutations were identified in 13 (34%) patients. The median age at the time of sequencing was 69.6 years. The distribution between males/females was similar. 10 (26%) were black, and the remaining were white. PPM1D(n=6) and DNMT3A mutations (n=6) were most frequently seen followed by TET2 (n=2) and BRCC3 (n=2). Essential hypertension and type 2 diabetes were present in 58% (n=22) and 30% (n=11) of patients, respectively, and a minority of patients had established coronary disease (n=3) or heart failure (n=1).

Conclusion:

These preliminary results from the CHIVE-IMPACT initiative demonstrate the feasibility and impact of establishing a CH biorepository in underserved areas. By leveraging local healthcare infrastructures and utilizing affordable targeted sequencing assay, we can establish and provide clinical trial access to underserved communities. As enrolled subjects came from community cancer centers, a natural, expected bias of prior chemotherapy exposure and increased rates of CH were detected. Still, understanding the natural history of CH in cancer patients in an underserved area addresses disparities in current efforts to prospectively monitor CH, and contribute valuable patient data to the growing field of CH research. Future directions include expanding the network of CHIVE-IMPACT clinics, further refining care protocols based on ongoing research findings, and developing clinical trials to address specific high-risk CH growth patterns.

Kishtagari:Syndex: Current equity holder in publicly-traded company; Rigel: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sevier Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron Coporation: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Bick:TenSixteen Bio: Consultancy. Savona:AbbVie; Bristol Myers Squibb; CTI BioPharma Corp.; Geron; Karyopharm; Novartis Pharmaceuticals Corporation; Ryvu Therapeutics; and Sierra Oncology, Inc.: Consultancy; Astex Pharmaceuticals for travel grant.: Other: Financial or Material Support; Empath Biosciences; Karyopharm and Ryvu Therapeutics: Current holder of stock options in a privately-held company; ALX Oncology Inc.; Astex Pharmaceuticals; Incyte Corporation; and Takeda Pharmaceutical Company Limited.: Research Funding.