Abstract
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.
Funder
University of Texas MD Anderson Cancer Center
K12 Paul Calabresi Clinical Oncology Scholar Award and the American Society of Hematology Junior Faculty Scholar Award in Clinical Research
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology
Cited by
13 articles.
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