Abstract 5925: Prevalence of clonal hematopoiesis in patients with monoclonal gammopathy of undetermined significance
Authors: Quaney Vianey , Kroger Benjamin , Sannareddy Aishwarya , Khan Umar , Kalkan Fatma , Collins Robert H. , Madanat Yazan F. , Vusirikala Madhuri , Huang Yi , Awan Farrukh T. , Ramakrishnan Praveen , Afrough Aimaz , Anderson Larry D. , Chung Stephen S. , Kaur Gurbakhash 
Published: April 2023

Abstract
INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the expansion of progeny derived from hematopoietic stem cells that have acquired somatic mutations at a VAF greater than 2%. CHIP manifests in 10% of patients older than 65 and is associated with an increased risk of progression to malignancies such as the MDS or AML. Although the risk factors for developing CHIP remain incompletely defined, they include prior exposure to chemotherapy and a history of smoking. Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the abnormal growth of clonal plasma cells in the bone marrow and carries a risk of 1% for progression to multiple myeloma (MM) per year. Like CHIP, it becomes more prevalent with age and is associated with smoking. Additionally, patients with MM have demonstrated an increased risk for malignancies. Thus, an examination for a correlation between CHIP and MGUS promises to reveal a link between these two pre-malignant conditions. A recent study did not demonstrate such an association, but this study was performed in a very elderly population and may not be applicable to younger patients. In this study, we aim to assess the relationship between CHIP and MGUS in a population-based cohort of MGUS patients seen at UT Southwestern Medical Center.
METHODS: To evaluate an association between CHIP and MGUS, we collected bone marrow samples from 37 patients diagnosed with MGUS. We employed a hybridization capture-based next generation sequencing assay in order to detect CHIP. We identified 24 genes known to cause CHIP in adults. We also evaluated patients risk for developing MM after having been diagnosed with CHIP.
RESULTS: The mean age was 68, (range 26-92). 22 patients were white, 8 were black and 3 Hispanic/Latino. 17 patients had IgG, 7 had IgA, 3 had IgM, 3 had biclonal gammopathy and 7 light-chain MGUS. We identified 18 mutations to validate the presence of CHIP in 10 (27%) patients, with the most frequent being DNMT3A (7 patients) and TET2 (5 patients). Other common mutations noted were PPM1D (2), GND1 (1), SF3B1 (1), ASXL1 in (1), and NRAS in (1). 3 out of the 10 patients harbored 2 mutations and 1 harbored 4 mutations. History of chemotherapy (n=6) and smoking (n=14) was taken into consideration to determine the relative risk of patients with MGUS developing CHIP. We found that those who had a prior history of smoking and chemotherapy displayed a higher risk of CHIP.
CONCLUSION: There was no significant association between CHIP and MM progression. Our analysis showed 1 patient with CHIP progression and 2 without CHIP progression. Because the rates of CHIP and MGUS are positively correlated with characteristics like aging and a history of smoking, we expected to see high rates of CHIP in patients within our cohort. However, our data suggests that CHIP is frequent (27%) in MGUS patients, but larger future cohorts need to be evaluated to validate this association.
Citation Format: Vianey Quaney, Benjamin Kroger, Aishwarya Sannareddy, Umar Khan, Fatma Kalkan, Robert H. Collins, Yazan F. Madanat, Madhuri Vusirikala, Yi Huang, Farrukh T. Awan, Praveen Ramakrishnan, Aimaz Afrough, Larry D. Anderson, Stephen S. Chung, Gurbakhash Kaur. Prevalence of clonal hematopoiesis in patients with monoclonal gammopathy of undetermined significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5925.