A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis

Tamanna Haque; Aditi Shastri; Pinkal Desai; Zhuoer Xie; Danielle Hammond; Zoe King; Ashwin Kishtagari; Yazan F Madanat; Yasmin Abaza; Alexander J Silver; Abhay Singh; Uma M Borate; J Brett Heimlich; David A Slosky; Kelly L Bolton; Mrinal S Patnaik; Alexander G Bick; Amit K Verma; Siddhartha Jaiswal; David P Steensma; Michael R Savona

doi:10.1111/bjh.19925

A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis

Br J Haematol. 2024 Dec 9. doi: 10.1111/bjh.19925. Online ahead of print.

Authors

Tamanna Haque¹, Aditi Shastri², Pinkal Desai³, Zhuoer Xie⁴, Danielle Hammond⁵, Zoe King², Ashwin Kishtagari⁶, Yazan F Madanat⁷, Yasmin Abaza⁸, Alexander J Silver⁶, Abhay Singh⁹, Uma M Borate¹⁰, J Brett Heimlich⁶, David A Slosky¹¹, Kelly L Bolton¹², Mrinal S Patnaik¹³, Alexander G Bick⁶, Amit K Verma², Siddhartha Jaiswal¹⁴, David P Steensma¹⁵, Michael R Savona⁶

Affiliations

¹ Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
² Division of Hematologic Malignancies, Department of Oncology, Montefiore-Einstein Comprehensive Cancer Center, Bronx, New York, USA.
³ Department of Medicine, Hematology/Oncology, Cornell University, New York, New York, USA.
⁴ Malignant Hematology Department, Moffit Cancer Center, Tampa, Florida, USA.
⁵ Department of Leukemia, MD Anderson Cancer Center, Houston, Texas, USA.
⁶ Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
⁷ Division of Hematology and Oncology, UT Southwestern, Dallas, Texas, USA.
⁸ Department of Medicine, Hematology and Oncology, Northwestern University, Chicago, Illinois, USA.
⁹ Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Division of Hematology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
¹¹ Division of Cardiology, Department of Medicine, University of Wisconsin Medical Center, Madison, Wisconsin, USA.
¹² Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
¹³ Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
¹⁴ Department of Pathology, Stanford University, Stanford, California, USA.
¹⁵ DP Steensma LLC, Cambridge, Massachusetts, USA.

PMID: 39653653
DOI: 10.1111/bjh.19925

Abstract

The age-associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy. Thoughtful consideration is needed to design trials that are both clinically relevant and avoid overmedicalization. Here, we summarize clinical studies of CH to date and provide suggestions and guidance on how to approach designing CH-focused therapeutic clinical trials. These recommendations are derived from discussions among clinical researchers and scientists emanating from the Inaugural Meeting on Somatic Mutations and Predisease in October 2021.

Keywords: clinical trials; clonal cytopenias; clonal hematopoiesis; therapy.

Publication types

Review