Characteristics and Outcomes of Patients With Multiple Myeloma Who Developed Therapy-Related Acute Myeloid Leukemia and Myelodysplastic Syndrome After Autologous Cell Transplantation

Abstract

Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing the therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1/1/2000 and 12/31/2018, and later developed t-MDS/AML. Among the 2982 patients that underwent at least one Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n=52; AML, n=3). The median age at t-MDS/AML diagnosis was 66 years (range, 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis was 58.5 months (range, 6-206 months). At diagnosis, all 3 patients with tAML and 65% of those with tMDS had high-risk disease, per ELN2022 and R-IPSS, respectively, and 62% had TP53 gene mutations. Patients who developed t-MDS/AML were older at MM diagnosis (median: 61 vs. 59 years; p=0.06), more often were male (73% vs. 58%; p=0.029), received more than 2 years of lenalidomide maintenance (57% vs. 39%; p=0.014) and experienced complete remission more frequently following Auto-HCT compared to those who did not develop t-MDS/AML (56% vs. 40%; p=0.012). In a multivariable model, male gender, advanced age at MM diagnosis, experiencing complete remission after Auto-HCT, and lenalidomide maintenance were independent predictors of developing t-MDS/AML. Among the patients who developed t-MDS/AML, 14 (25%) underwent allogeneic hematopoietic stem transplant (Allo-HCT). After a median follow-up of 9.9 months from t-MDS/AML diagnosis, the median overall survival (OS) after t-MDS/AML diagnosis was 11.8 months for all patients, and 18.2 months vs. 11.1 months for Allo-HCT recipients vs. nonrecipients, respectively (P=0.25). On univariate analysis, receiving an alkylator as induction for MM (hazard ratio [95% CI]: 2.9 [1.3-6.3]; P=0.009), age > 60 years (3.1 [1.2-8.2]; P=0.025), and higher risk R-IPSS (2.7 [1.3-6.0]; P=0.011) predicted worse OS after t-MDS/AML diagnosis. None of these retained significance in the multivariable analysis. T-MDS/AML following an Auto-HCT for MM is associated with aggressive disease characteristics, including high risk cytogenetics and TP53 mutations. The outcomes of patients remain poor, even with Allo-HCT. A better understanding of disease biology and novel therapeutic approaches is warranted.