TY - JOUR
T1 - Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia
AU - Kadia, Tapan M.
AU - Ravandi, Farhad
AU - Molica, Matteo
AU - Bataller, Alex
AU - Borthakur, Gautam
AU - Daver, Naval
AU - Jabbour, Elias
AU - DiNardo, Courtney D.
AU - Pemmaraju, Naveen
AU - Jain, Nitin
AU - Ferrajoli, Alessandra
AU - Ylimaz, Musa
AU - Bose, Prithviraj
AU - Tidwell, Rebecca Slack
AU - Marx, Kayleigh R.
AU - Rausch, Caitlin R.
AU - Kanagal-Shamanna, Rashmi
AU - Wang, Sa
AU - Islam, Rabiul
AU - Champlin, Richard
AU - Shpall, Elizabeth
AU - Konopleva, Marina
AU - Garcia-Manero, Guillermo
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/11
Y1 - 2023/11
N2 - The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1–5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21–65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.
AB - The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1–5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). The median age was 55 years (range, 21–65). CR + CRi was 83% (54/65) and 27% in the untreated and ts-AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3-ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow-up of 76 months, the 2- and 4-year OS of 57% and 50% compared to 20%, and 13% for ts-AML, respectively. Patients treated with CLIA+sorafenib had 2- and 5-year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival.
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U2 - 10.1002/ajh.27054
DO - 10.1002/ajh.27054
M3 - Article
C2 - 37635400
AN - SCOPUS:85168923640
SN - 0361-8609
VL - 98
SP - 1711
EP - 1720
JO - American journal of hematology
JF - American journal of hematology
IS - 11
ER -