Study Explores Risk Factors for Therapy-Related MDS, AML Following HCT for Multiple Myeloma

A study published in Transplantation and Cellular Therapy found that older age at multiple myeloma diagnosis and male gender were associated with a higher risk of developing treatment-related myelodysplastic syndromes (t-MDS) or acute myeloid leukemia (AML) following autologous hematopoietic cell transplantation (auto-HCT) for multiple myeloma.

Undergoing high-dose chemotherapy (HDT) and auto-HCT for multiple myeloma is known to increase the risk of developing second primary malignancies (SPMs), including t-MDS and AML, the authors noted. Their study aimed to determine which patients appear to be at the highest risk of developing t-MDS or AML, as well as characterize outcomes among patients who develop these secondary malignancies following HDT for multiple myeloma.

A total of 2982 patients who underwent at least 1 auto-HCT for multiple myeloma were included in the study, and 55 (2%) of those patients developed t-MDS (n = 52) or AML (n = 3). The median patient age was 59 years (range, 22-82), and most patients were male (58%).

The median time from auto-HCT to SPM diagnosis was 58.5 months (range, 6-206), and the median age at SPM diagnosis was 66 years (range, 43-83). All patients with AML and 65% of patients with t-MDS had high-risk disease characteristics as defined by European LeukemiaNet 2022 classification for AML and the Revised International Prognostic Scoring System (R-IPSS) for MDS. Overall, 62% of patients had TP53 gene mutations, which are considered risk factors for adverse outcomes, according to the authors.

Those who had SPMs diagnosed were older at the time of multiple myeloma diagnosis (median age of 61 vs 59 years; P = .06). Patients who developed SPMs were also more often male (73% vs 58%; P = .029) and underwent more than 2 years of lenalidomide maintenance therapy (57% vs 39%; P = 0.014). Complete remission following auto-HCT was also more common among those who developed SPMs vs those who did not (56% vs 40%; P = .012).

These factors were found to be independently predictive of SPM development in a multivariable model. Among 14 patients with SPMs who received allogeneic rather than auto=HCT, overall survival (OS) was 18.2 vs 11.1 months in nonrecipients (P = .25).

Although univariate analyses found that receiving an alkylator as induction for multiple myeloma, age older than 60 years, and higher risk R-IPSS predicted worse OS after t-MDS/AML diagnosis, these factors did not show significance in the multivariable analysis.

“In summary, our results indicate that advanced age at diagnosis of MM and male gender increase the risk for developing t-MDS/AML after HDT/auto-HCT,” the authors concluded. “The development of t-MDS/AML in this setting is associated with adverse disease characteristics, including poor-risk cytogenetic and molecular features. The outcome is dismal regardless of receipt of an allo-HCT.”

Study limitations included its retrospective nature, which introduces potential for selection bias and missing data. Inconsistency in the treatment of patients who develop SPMs is another limitation of the study, as well as a lack of information on mobilizing agents used ahead of autograft collection before HDT or auto-HCT, the authors noted.

Overall, the findings support further research into the risk factors for SPM development among patients with multiple myeloma undergoing HCT. This could help facilitate early screening and possibly prevention of SPMs, including t-MDS and AML.

Reference

Yalniz FF, Greenbaum U, Pasvolsky O, et al. Characteristics and outcomes of patients with multiple myeloma who developed therapy-related acute myeloid leukemia and myelodysplastic syndrome following autologous cell transplantation. Transplant Cell Ther. Published online July 10, 2023. doi:10.1016/j.jtct.2023.06.015