Impact of Frontline Treatment Approach on Outcomes in Patients With Secondary AML With Prior Hypomethylating Agent Exposure

Authors

Nicholas J Short
Sangeetha Venugopal
Wei Qiao
Tapan M Kadia
Farhad Ravandi
Walid Macaron
Courtney D Dinardo
Naval Daver
Marina Konopleva
Gautam Borthakur
Elizabeth J Shpall
Uday Popat
Richard E Champlin
Rohtesh Mehta
Gheath Al-Atrash
Betul Oran
Elias Jabbour
Guillermo Garcia-Manero
Ghayas C Issa
Guillermo Montalban-Bravo
Musa Yilmaz
Abhishek Maiti
Hagop Kantarjian

Publication Date

1-29-2022

Journal

Journal of Hematology & Oncology

Abstract

BACKGROUND: Treated secondary acute myeloid leukemia (ts-AML)-i.e., AML arising from a previously treated antecedent hematologic disorder-is associated with very poor outcomes. The optimal frontline treatment regimen for these patients is uncertain.

METHODS: We retrospectively analyzed 562 patients who developed AML from preceding myelodysplastic syndrome or chronic myelomonocytic leukemia for which they had received a hypomethylating agent (HMA). Patients with ts-AML were stratified by frontline AML treatment with intensive chemotherapy (IC, n = 271), low-intensity therapy (LIT) without venetoclax (n = 237), or HMA plus venetoclax (n = 54).

RESULTS: Compared with IC or LIT without venetoclax, HMA plus venetoclax resulted in higher CR/CRi rates (39% and 25%, respectively; P = 0.02) and superior OS (1-year OS 34% and 17%, respectively; P = 0.05). The benefit of HMA plus venetoclax was restricted to patients with non-adverse risk karyotype, where HMA plus venetoclax resulted in a median OS of 13.7 months and 1-year OS rate of 54%; in contrast, for patients with adverse risk karyotype, OS was similarly dismal regardless of treatment approach (median OS 3-5 months). A propensity score analysis accounting for relevant clinical variables confirmed the significant OS benefit of HMA plus venetoclax, as compared with other frontline treatment approaches. In a landmark analysis, patients with ts-AML who underwent subsequent hematopoietic stem cell transplantation (HSCT) had superior 3-year OS compared to non-transplanted patients (33% vs. 8%, respectively; P = 0.003).

CONCLUSIONS: The outcomes of ts-AML are poor but may be improved with use of an HMA plus venetoclax-based regimen, followed by HSCT, particularly in those with a non-adverse risk karyotype.

Keywords

Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bridged Bicyclo Compounds, Heterocyclic, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Male, Middle Aged, Myelodysplastic Syndromes, Neoplasms, Second Primary, Retrospective Studies, Sulfonamides, Young Adult, Acute myeloid leukemia, Azacitidine, Decitabine, Myelodysplastic syndrome, Chronic myelomonocytic leukemia

DOI

10.1186/s13045-022-01229-z

PMID

35093134

PMCID

PMC8800349

PubMedCentral® Posted Date

1-29-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes