Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML
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 cytarabin...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 February 2024
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| In: |
Leukemia
Year: 2024, Volume: 38, Issue: 4, Pages: 762-768 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-024-02175-0 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41375-024-02175-0 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41375-024-02175-0 
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| Author Notes: | Shai Shimony, Jan Philipp Bewersdorf, Rory M. Shallis, Yiwen Liu, Eva J. Schaefer, Amer M. Zeidan, Aaron D. Goldberg, Eytan M. Stein, Guido Marcucci, R. Coleman Lindsley, Evan C. Chen, Jorge Ramos Perez, Anthony Stein, Daniel J. DeAngelo, Donna S. Neuberg, Richard M. Stone, Brian Ball and Maximilian Stahl |
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| 245 | 1 | 0 | |a Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML |c Shai Shimony, Jan Philipp Bewersdorf, Rory M. Shallis, Yiwen Liu, Eva J. Schaefer, Amer M. Zeidan, Aaron D. Goldberg, Eytan M. Stein, Guido Marcucci, R. Coleman Lindsley, Evan C. Chen, Jorge Ramos Perez, Anthony Stein, Daniel J. DeAngelo, Donna S. Neuberg, Richard M. Stone, Brian Ball and Maximilian Stahl |
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| 520 | |a 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. | ||
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