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

Authors

Fevzi F Yalniz
Uri Greenbaum
Oren Pasvolsky
Denái R Milton
Rashmi Kanagal-Shamanna
Jeremy Ramdial
Samer Srour
Rohtesh Mehta
Amin Alousi
Uday R Popat
Yago Nieto
Partow Kebriaei
Gheath Al-Atrash
Betul Oran
Chitra Hosing
Sairah Ahmed
Richard E Champlin
Elizabeth J Shpall
Muzaffar H Qazilbash
Qaiser Bashir

Language

English

Publication Date

2-1-2024

Journal

Transplantation and Cellular Therapy

DOI

10.1016/j.jtct.2023.06.015

PMID

37437764

Abstract

Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing 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 January and 31 December 2018 and later developed t-MDS/AML. Among the 2982 patients who underwent at least 1 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 therapy-related myelodysplastic syndrome (tMDS) had high-risk disease, per 2022 European LeukemiaNet and R-IPSS, respectively, and 62% had TP53 gene mutations. Patients who developed tMDS/AML were older at MM diagnosis (median 61 versus 59 years; P = .06), more often were male (73% versus 58%; P = .029), received more than 2 years of lenalidomide maintenance (57% versus 39%; P = .014), and experienced complete remission more frequently after Auto-HCT compared to those who did not develop t-MDS/AML (56% versus 40%; P = .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 transplantation (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 versus 11.1 months for Allo-HCT recipients versus nonrecipients, respectively (P = .25). On univariate analysis, receiving an alkylator as induction for MM (hazard ratio [95% confidence interval]: 2.9 [1.3-6.3]; P = .009), age > 60 years (3.1 [1.2-8.2]; P = .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 after 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.

Keywords

Humans, Male, Adult, Middle Aged, Aged, Aged, 80 and over, Female, Multiple Myeloma, Lenalidomide, Retrospective Studies, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Allogeneic, Autologous, Cell transplantation, Multiple myeloma, Myeloid malignancy

Published Open-Access

yes

Recommended Citation

Yalniz, Fevzi F; Greenbaum, Uri; Pasvolsky, Oren; et al., "Characteristics and Outcomes of Patients With Multiple Myeloma Who Developed Therapy-Related Acute Myeloid Leukemia and Myelodysplastic Syndrome After Autologous Cell Transplantation" (2024). Faculty, Staff and Student Publications. 5249.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5249