TY - JOUR
T1 - Long-term results of low-intensity chemotherapy with clofarabine or cladribine combined with low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia
AU - Kadia, Tapan M.
AU - Ravandi, Farhad
AU - Borthakur, Gautam
AU - Konopleva, Marina
AU - DiNardo, Courtney D.
AU - Daver, Naval
AU - Pemmaraju, Naveen
AU - Kanagal-Shamanna, Rashmi
AU - Wang, Xuemei
AU - Huang, Xuelin
AU - Pierce, Sherry
AU - Rausch, Caitlin
AU - Burger, Jan
AU - Ferrajoli, Alessandra
AU - Jain, Nitin
AU - Popat, Uday
AU - Estrov, Zeev
AU - Verstovsek, Srdan
AU - Jabbour, Elias
AU - Garcia-Manero, Guillermo
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - The treatment of older patients with newly diagnosed acute myeloid leukemia (AML) using intensive chemotherapy is associated with treatment intolerance and poor survival. We evaluated two new lower-intensity regimens with clofarabine (n = 119) or cladribine (n = 129) combined with low-dose cytarabine (LDAC) alternating with decitabine. We reviewed response rates by subgroup and long term outcomes of 248 patients with newly diagnosed non core-binding-factor AML treated on two clinical trials investigating double nucleoside-analogue therapy (DNT) alternating with HMA from October, 2008 to April, 2018. Of 248 patients with a median age of 69 years (range, 49–85 years), 102 patients (41%) were ≥ 70 years, and 108 (44%) had adverse karyotype. Overall, 164 patients (66%) responded: 147 (59%) complete remission (CR) and 17 (7%) CR with incomplete count recovery (CRi). With a median follow up of 60 months, median relapse-free and overall survival (OS) were 10.8 and 12.5 months, respectively. The 2-year OS was 29%. Among patients with normal karyotype, the CR/CRi rate was 79% and the median OS 19.9 months. High response rates and OS were observed in patients with mutations in NPM1, FLT3, IDH2, and RUNX1. The 4- and 8-week mortality rates were 2% and 11%, respectively. The backbone of clofarabine or cladribine and LDAC alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed AML. Incorporating targeted therapies could extend the efficacy of this approach and provide more curative therapeutic options in this AML population.
AB - The treatment of older patients with newly diagnosed acute myeloid leukemia (AML) using intensive chemotherapy is associated with treatment intolerance and poor survival. We evaluated two new lower-intensity regimens with clofarabine (n = 119) or cladribine (n = 129) combined with low-dose cytarabine (LDAC) alternating with decitabine. We reviewed response rates by subgroup and long term outcomes of 248 patients with newly diagnosed non core-binding-factor AML treated on two clinical trials investigating double nucleoside-analogue therapy (DNT) alternating with HMA from October, 2008 to April, 2018. Of 248 patients with a median age of 69 years (range, 49–85 years), 102 patients (41%) were ≥ 70 years, and 108 (44%) had adverse karyotype. Overall, 164 patients (66%) responded: 147 (59%) complete remission (CR) and 17 (7%) CR with incomplete count recovery (CRi). With a median follow up of 60 months, median relapse-free and overall survival (OS) were 10.8 and 12.5 months, respectively. The 2-year OS was 29%. Among patients with normal karyotype, the CR/CRi rate was 79% and the median OS 19.9 months. High response rates and OS were observed in patients with mutations in NPM1, FLT3, IDH2, and RUNX1. The 4- and 8-week mortality rates were 2% and 11%, respectively. The backbone of clofarabine or cladribine and LDAC alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed AML. Incorporating targeted therapies could extend the efficacy of this approach and provide more curative therapeutic options in this AML population.
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U2 - 10.1002/ajh.26206
DO - 10.1002/ajh.26206
M3 - Article
C2 - 33901324
AN - SCOPUS:85106441917
SN - 0361-8609
VL - 96
SP - 914
EP - 924
JO - American journal of hematology
JF - American journal of hematology
IS - 8
ER -