DNA methylation in peripheral blood mononuclear cells (PBMCs) may be a novel biomarker in multiple myeloma (MM), demonstrating associations with disease control and patient functional status and socioeconomic adversity, according to a correspondence published in Bone Marrow Transplant.
Researchers conducted a follow-up study of BMT CTN 0702 (STaMINA), a phase 3 clinical trial that compared outcomes of 758 patients with MM randomly assigned after standard-of-care high-dose melphalan conditioning, autologous hematopoietic cell transplantation (AHCT), and posttransplant lenalidomide maintenance (ClinicalTrials.gov Identifier: NCT01109004).
In the new study, the team evaluated the relationship between global DNA methylation in PBMCs and baseline characteristics and patient-reported outcomes of patients from STaMINA. Patients previously completed the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the 36-Item Short Form Survey (SF-36) to assess symptom burden and quality of life (QoL). Study participants had PBMCs collected and completed the FACT-BMT and SF-36 at STaMINA enrollment and 1 year.
A total of 232 patients, 62% males and 15% African Americans, were included in the analysis. The mean patient age was 56 years. The researchers noted good functional status with Karnofsky performance status (KPS) score ≥90% in 74% of patients, a comorbidity score ≥3 in 32%, and high-risk disease in 29%.
For disease control with pretransplant induction therapy, they observed a very good partial response or better in 48% and partial response (PR) or worse in 52% of patients. The analysis included only patients who responded at 1 year post-AHCT because patients who progressed discontinued the study and stopped reporting FACT-BMT.
At baseline, the researchers demonstrated significantly higher PBMC DNA methylation levels in patients with the stable or progressive disease versus patients with PR or better (P =.014) as well as in patients with lower versus higher KPS (P=.011), lower versus higher educational background (P =.01), and work status of employed versus not employed (P =.05).
The investigators also evaluated change in PBMC DNA methylation levels at 1 year post AHCT. They found that methylation levels decreased by 73%, from a mean (standard deviation) of 0.33 (0.27) at baseline to 0.09 (0.06) at 1 year (P <.001).
At that time, they observed improvements in mean FACT scores (FACT-G, FACT- BMT, FACT-BMTS, and FACT-BMT TOI; P <10-3 for all). They also observed improvements in the Physical Well-Being, Emotional Well-Being, and Functional Well-Being subscales (P <.001).
At 1 year, they observed reductions in PBMC DNA methylation in subgroups with high baseline values, specifically pre-AHCT stable and progressive disease (P =.011) and high school or less education (P =.02). They observed non-significant trends for reductions in KPS (P =.056) and employment status (P =.082) as well.
“The finding that these disadvantaged groups exhibited the greatest reduction in methylation scores at 1 year post AHCT strengthened the contention that global DNA
methylation in PBMCs may be a valuable biomarker of treatment response and recovery in myeloma,” the researchers concluded in their report.
Limitations of the study included the heterogeneity and variability of PBMC
cell types, which exhibit different epigenomic profiles including methylation patterns, and the need to supplement global DNA methylation scores with genome-wide DNA methylation assays able to identify driver genes.
D’Souza A, Brazauskas R, Teng BQ, et al. DNA methylation in circulating leukocytes is a novel biomarker in multiple myeloma. Bone Marrow Transplant. Published online December 2, 2022. doi:10.1038/s41409-022-01887-0