TY - JOUR
T1 - Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
AU - Kadia, Tapan M.
AU - Reville, Patrick K.
AU - Wang, Xuemei
AU - Rausch, Caitlin R.
AU - Borthakur, Gautam
AU - Pemmaraju, Naveen
AU - Daver, Naval G.
AU - Dinardo, Courtney D.
AU - Sasaki, Koji
AU - Issa, Ghayas C.
AU - Ohanian, Maro
AU - Montalban-Bravo, Guillermo
AU - Short, Nicholas J.
AU - Jain, Nitin
AU - Ferrajoli, Alessandra
AU - Bhalla, Kapil N.
AU - Jabbour, Elias
AU - Takahashi, Koichi
AU - Malla, Rashmi
AU - Quagliato, Kelly
AU - Kanagal-Shamanna, Rashmi
AU - Popat, Uday R.
AU - Andreeff, Michael
AU - Garcia-Manero, Guillermo
AU - Konopleva, Marina Y.
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - PURPOSEThe combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.METHODSThis is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity.RESULTSA total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome.CONCLUSIONVenetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non-anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted.
AB - PURPOSEThe combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.METHODSThis is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity.RESULTSA total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome.CONCLUSIONVenetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non-anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted.
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U2 - 10.1200/JCO.21.02823
DO - 10.1200/JCO.21.02823
M3 - Article
C2 - 35704787
AN - SCOPUS:85133680961
SN - 0732-183X
VL - 374
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
M1 - JCO.21.02823
ER -