Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML Journal Article

  

Authors:	Shimony, S.; Bewersdorf, J. P.; Shallis, R. M.; Liu, Y.; Schaefer, E. J.; Zeidan, A. M.; Goldberg, A. D.; Stein, E. M.; Marcucci, G.; Lindsley, R. C.; Chen, E. C.; Ramos Perez, J.; Stein, A.; DeAngelo, D. J.; Neuberg, D. S.; Stone, R. M.; Ball, B.; Stahl, M.
Article Title:	Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
Abstract:	Molecularly defined secondary acute myeloid leukemia is associated with a prior myeloid neoplasm and confers a worse prognosis. We compared outcomes of molecularly defined secondary AML patients (n = 395) treated with daunorubicin and cytarabine (7 + 3, n = 167), liposomal daunorubicin and cytarabine (CPX-351, n = 66) or hypomethylating agents (HMA) + venetoclax (VEN) (n = 162). Median overall survival (OS) was comparable between treatment groups among patients aged >60 years. In a multivariable model HMA + VEN vs. 7 + 3 was associated with better OS (hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.42–0.98, p = 0.041]), whereas CPX-351 vs. 7 + 3 was not (HR 0.79 [CI 95% 0.50–1.25, p = 0.31]). Allogeneic hematopoietic stem cell transplantation, BCOR and IDH mutations were associated with improved OS; older age, prior myeloid disease, NRAS/KRAS mutations, EZH2 mutation, and monosomal karyotype were associated with worse OS. When analyzed in each treatment separately, the IDH co-mutations benefit was seen with 7 + 3 and the detrimental effect of NRAS/KRAS co-mutations with HMA + VEN and CPX-351. In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1 mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations. © The Author(s), under exclusive licence to Springer Nature Limited 2024.
Keywords:	adult; aged; retrospective studies; young adult; gene mutation; major clinical study; overall survival; genetics; leukemia, myeloid, acute; cytarabine; antineoplastic agent; gene; antineoplastic combined chemotherapy protocols; cohort analysis; retrospective study; age; myelodysplastic syndrome; sulfonamide; sulfonamides; daunorubicin; allogeneic hematopoietic stem cell transplantation; neoplasms, second primary; oncogene k ras; fused heterocyclic rings; protein p21; proto-oncogene proteins p21(ras); myeloproliferative neoplasm; induction chemotherapy; ezh2 gene; oncogene n ras; idh1 gene; idh2 gene; acute myeloid leukemia; very elderly; humans; human; male; female; article; venetoclax; cytarabine plus daunorubicin; cpx-351; bridged bicyclo compounds, heterocyclic; bcor gene; second primary neoplasm
Journal Title:	Leukemia
Volume:	38
Issue:	4
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	2024-04-01
Start Page:	762
End Page:	768
Language:	English
DOI:	10.1038/s41375-024-02175-0
PUBMED:	38378841
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185329260&doi=10.1038%2fs41375-024-02175-0&partnerID=40&md5=37f39c9a705a04de4e3fa491f350add5
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/215826