In a review in the journal Seminars in Oncology, researchers detailed the relevance of clonal hematopoiesis (CH) to multiple myeloma (MM), in terms of epidemiology, disease characteristics, and treatment considerations. The review was authored by Christin B. DeStefano, MD, of David Grant US Air Force Medical Center in Fairfield, California, and colleagues.
According to Dr DeStefano and colleagues, the first description of CH occurred 25 years ago, but data regarding its significance to MM have just recently begun to be understood. The prevalence of CH in patients with MM has been evaluated in a few studies, with rates such as 33% of newly diagnosed patients having CH in 1 study, and 21.6% of patients having CH with a variant allele fraction of ≥1% at the time of high-dose melphalan plus autologous stem cell transplantation (HDM-ASCT) in another study.
CH is linked to poorer survival in patients with MM, in terms of both overall survival (OS) and progression-free survival, according to research highlighted in the review. They explained that the relationship between CH and poorer survival is based on an increase in MM progression. Among specific mutations seen with CH, the DNMT3A p.R882 mutation was especially linked to worse survival, being associated with a median OS of 1 year.
Treatment with HDM-ASCT is also associated with worse prognosis with CH, which the authors suggested is related to potential genotoxicity with melphalan. However, lenalidomide maintenance therapy appears associated with better survival outcomes following HDM-ASCT. To illustrate this point, the authors described the results of a study in which the median OS was 3.6 years for patients with MM and CH who were treated with HDM-ASCT and no lenalidomide maintenance, compared with 6.6 years for patients without CH and no lenalidomide maintenance (P =.013). However, patients who received lenalidomide maintenance showed similar median OS times regardless of the presence (7.7 years) or absence of CH (8.9 years; P =.49).
The authors noted that many aspects of the relationship between CH and MM remain unknown. Current research is evaluating the importance of CH of indeterminate potential in monoclonal gammopathy of unknown significance and in smoldering myeloma. Also, impacts of CH on therapy-related myeloid neoplasms, cardiovascular events, and other nonrelapse-related outcomes with MM require further study, according to the researchers.
“In the MM research community, it is becoming increasingly recognized that successful therapy requires accounting for much more than the malignant plasma cell itself, and our understanding of clonal hematopoiesis and its investigation in this disease is actively contributing to this complexity,” the authors wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
DeStefano CB, Gibson SJ, Sperling AS, Richardson PG, Ghobrial I, Mo CC. The emerging importance and evolving understanding of clonal hematopoiesis in multiple myeloma. Semin Oncol. Published online January 20, 2022. doi:10.1053/j.seminoncol.2022.01.009