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    Nursing and Allied Health Symposium

    Category: Nursing & Allied Health Symposium

    Clonal Hematopoiesis in Multiple Myeloma: Current Implications and Future Directions

    (NSP-11) Clonal Hematopoiesis in Multiple Myeloma: Current Implications and Future Directions

    Thursday, September 18, 2025
    Introduction: Clonal Hematopoiesis of Indeterminate potential (CHIP) is an emerging area of interest in multiple myeloma (MM) due to potential association with poorer outcomes, early relapse and increased risk of treatment related myeloid neoplasm (TMN). As MM treatments improve and survival increases, CHIP will be identified more frequently due to better testing. CHIP is defined by age-dependent accumulation of somatic leukemia-associated driver mutations in hematopoietic stem cells in individuals with normal blood counts and no underlying myeloid neoplasm. This review summarizes recent literature on the topic to define areas of consensus, uncertainty and future directions for prospective studies to assess CHIP in MM.

    Methods: PubMed was searched using terms clonal hematopoiesis, indeterminate potential and multiple myeloma. Inclusion criteria: publication 2020 or later, specific focus on CHIP in MM and addressing auto stem cell transplant (ASCT) and/or maintenance excluding immunotherapy. Of 96 identified articles, 18 met criteria for full review.

    Results: Three retrospective cohort studies of CHIP in MM were identified. In one study, 629 patients receiving ASCT, CHIP was detected in 21.6%.  Of patients receiving first-line immunomodulatory drugs (IMIDs), 3.3% developed TMN. IMID maintenance improved progression free survival (PFS) and overall survival (OS) regardless of CHIP. OS was lower in CHIP positive patients not receiving IMID maintenance due to disease progression. In another cohort of 101 patients 23% had CHIP at diagnosis. ASCT and IMID maintenance were given to 43% of CHIP positive and 38% of CHIP negative patients and no difference in PFS, OS, or TMN were observed. In the CoMMpass study, (986 ASCT eligible and ineligible patients) CHIP was present in 10% at diagnosis and increased to 25% over 3 years. No significant association was found with advanced R-ISS, high-risk cytogenetics or inferior PFS/OS regardless of ASCT. IMID maintenance provided benefit independent of CHIP status. CHIP was associated with increased risk of cardiovascular disease (CVD) and infections. In smaller studies suggested possible impact of CHIP on CAR-T response, earlier progression, cardiovascular events (CVD, HF, stroke), venous thromboembolism (VTE), stem cell mobilization and platelet engraftment.

    Conclusions: As MM patient survival improves understanding the clinical implications of CHIP is increasingly important. While CHIP may contribute to adverse outcomes, these risks may be mitigated by the use of IMID maintenance and ASCT may not worsen CHIP associated TMN. Additionally, CHIP may influence treatment response, count recovery, CVD, stroke and VTE. Prospective research is needed to define clinically relevant variant allele frequency thresholds, assess the impact of specific CHIP mutations (alone and in combination) and clarify their role in secondary malignancy and TMN risk. Improved understanding of CHIP in MM may lead to risk adapted strategies to reduce harm and optimize outcomes.