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Review
. 2025 Feb;206(2):416-427.
doi: 10.1111/bjh.19925. Epub 2024 Dec 9.

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

Tamanna Haque  1 , Aditi Shastri  2 , Pinkal Desai  3 , Zhuoer Xie  4 , Danielle Hammond  5 , Zoe King  2 , Ashwin Kishtagari  6 , Yazan F Madanat  7 , Yasmin Abaza  8 , Alexander J Silver  6 , Abhay Singh  9 , Uma M Borate  10 , J Brett Heimlich  6 , David A Slosky  11 , Kelly L Bolton  12 , Mrinal S Patnaik  13 , Alexander G Bick  6 , Amit K Verma  2 , Siddhartha Jaiswal  14 , David P Steensma  15 , Michael R Savona  6
Affiliations
Review

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

Tamanna Haque et al. Br J Haematol. 2025 Feb.

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.

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Conflict of interest statement

TH has served on advisory boards for Servier Pharmaceuticals, Morphosys and Bristol Myers Squibb. AS has received research funding from Kymera Therapeutics, advisory board fees from Gilead Sciences, Rigel Pharmaceuticals and Kymera Therapeutics, consultancy fees from Janssen Pharmaceuticals and honoraria from NACE & PeerView. PD has received research funding from Kura Oncology, Janssen Pharmaceuticals, BMS and has received consultancy fees for Servier Pharmaceuticals, BMS, Abbvie/Genentech. DH has received research funding from Break Through Cancer, funding for AML‐CHIP TeamLab. UMB received grants/research support from Abbvie, Incyte, Jazz, Pfizer; served on an advisory board for Abbvie, Genentech, Agios, Novartis, Blueprint, Astellas, Takeda, Kura, Servier; and received honorarium from RUNX1 foundation. YFM has received honoraria/consulting fees from BMS, Kura Oncology, BluePrint Medicines, Geron, OncLive and MD Education, VJHemOnc and Medscape Live. YFM participated in advisory boards and received honoraria from Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis. YFM received travel reimbursement from Blueprint Medicines, MD Education and Morphosys. None of these relationships were related to this work. YA served on scientific advisory boards or consults for: Astellas, Bristol Myers Squibb, Geron, KiTE, Pfizer, Rigel and Servier. YA received institutional trial support from AbbVie, ALX Oncology, Biomea, Biosight, Curis and Novartis. KLB received research funding and served on a medical advisory board of Servier. MSP served on advisory boards for CT1 and Astra Zeneca and received research funding from Stem Line, Kura Oncology, Polaris, Epigenetix, Solutherapeutics. AKV has received research funding from Prelude, BMS, GSK, Incyte, Medpacto, Curis and Eli Lilly and is a scientific advisor for Stelexis, Novartis, Acceleron and Celgene and received honoraria from Stelexis and Janssen and held equity in Stelexis and Throws Exception. SJ reported consultancies at Novartis, Roche Genentech, Astrazeneca; speaking fees from GSK and Merck; scientific advisory board membership and equity at Bitterroot Bio and at TenSixteen Bio, all unrelated to the present work. AGB is a scientific advisor and has received personal fees and equity in TenSixteen Bio. DPS is currently employed at Ajax Therapeutics. MRS has consulted and served on advisory boards for and/or received travel expenses from BMS, CTI, Forma, Geron, GSK, Rigel, Taiho and Treadwell; is an equity holder in and served on advisory committees for Empath Biosciences, Karyopharm and Ryvu; and received research funding from ALX Oncology, Astex, Incyte and Takeda. ZK, ZX, AK, AS, AS, JBH, DAS have no disclosures to report.

Figures

FIGURE 1
FIGURE 1
Evolution of CHIP to myeloid neoplasms. Most patients with CHIP do not develop myeloid neoplasia. However, the risk of transformation increases with the acquisition of certain clinical features, such as clonal CCUS, clonal monocytosis of undetermined significance or clonal cytopenia(s) and monocytosis of undetermined significance. Both intrinsic and extrinsic factors related to CHIP may contribute to the progression of myeloid disease. AML, acute myeloid leukaemia; CCUS, clonal cytopenia (s) of undetermined significance; CHIP, clonal haematopoiesis of indeterminate potential; DNA, deoxyribonucleic acid; HSC, haematopoietic stem cell; MDS, myelodysplastic neoplasm. [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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