Patients with monoclonal gammopathy of undetermined significance or smoldering multiple myeloma are at a higher risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia compared to the general population. This risk increases further in patients with multiple myeloma (MM) undergoing myeloma-specific treatments.

An analysis involving patients with MM who subsequently developed therapy-related MDS (t-MDS) between January 2017 and March 2020 reveals that treatments, particularly lenalidomide, may encourage the growth of pre-existing myeloid subclones harboring TP53 mutations, increasing the risk of t-MDS. These subclones, detectable years before t-MDS diagnosis, suggest a pre-existing vulnerability that may be exacerbated by MM treatments. This finding underscores the importance of monitoring and possibly adjusting therapeutic strategies for MM patients with detectable TP53 myeloid subclones to mitigate the risk of developing severe myeloid neoplasms. The data highlights the complex interplay between treatment, genetic predisposition, and the development of secondary malignancies in cancer therapy.

Reference: Escure G, Fournier E, Saade C, et al. Small myeloid subclones are present at diagnosis of multiple myeloma in patients who develop secondary myelodysplastic syndromes. Haematologica. 2024 Apr 1;109(4):1289-1292. doi: 10.3324/haematol.2023.284050. PMID: 37855058; PMCID: PMC10985426.