TY - JOUR
T1 - Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure
AU - Short, Nicholas J.
AU - Venugopal, Sangeetha
AU - Qiao, Wei
AU - Kadia, Tapan M.
AU - Ravandi, Farhad
AU - Macaron, Walid
AU - Dinardo, Courtney D.
AU - Daver, Naval
AU - Konopleva, Marina
AU - Borthakur, Gautam
AU - Shpall, Elizabeth J.
AU - Popat, Uday
AU - Champlin, Richard E.
AU - Mehta, Rohtesh
AU - Al-Atrash, Gheath
AU - Oran, Betul
AU - Jabbour, Elias
AU - Garcia-Manero, Guillermo
AU - Issa, Ghayas C.
AU - Montalban-Bravo, Guillermo
AU - Yilmaz, Musa
AU - Maiti, Abhishek
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - Azacitidine
KW - Chronic myelomonocytic leukemia
KW - Decitabine
KW - Myelodysplastic syndrome
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U2 - 10.1186/s13045-022-01229-z
DO - 10.1186/s13045-022-01229-z
M3 - Article
C2 - 35093134
AN - SCOPUS:85123905455
SN - 1756-8722
VL - 15
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 12
ER -