CLIA Chemotherapy With or Without Sorafenib as Frontline Treatment for Patients With AML

Results from a Phase 2 Trial

According to findings from a phase 2 trial published in the American Journal of Hematology, cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) standard chemotherapy with or without the addition of sorafenib yielded encouraging efficacy as a frontline treatment for patients with various subsets of acute myeloid leukemia (AML). 

CLIA with sorafenib yielded high rates of durable remission and excellent long-term survival among patients with newly diagnosed FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutated AML. CLIA was found to be safe and effective in young, fit patients with newly diagnosed AML, though it demonstrated inferior outcomes among patients with AML arising from previously treated myelodysplastic syndromes (ts-AML). 

This study included a total of 80 patients ≤65 years old with AML who were fit to receive intensive therapy, consisting of 65 patients with newly diagnosed AML and 15 with AML brought on by previously treated myelodysplastic syndrome, or treated secondary AML. Tapan M Kadia, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors aimed to examine the efficacy and safety outcomes of CLIA chemotherapy, as well as combined with sorafenib, in this patient population. 

Patients received cladarabine at 5 mg and cytarabine at 1 g/m2 on days 1 through 5, and idarubicin at 10 mg/m2 on days 1 through 3. Sorafenib was added to this treatment for patients with FLT3-ITD mutated AML. Results indicated that the complete remission (CR)/complete remission with incomplete count (CRi) was 83% among patients with untreated AML, and 27% among patients with ts-AML. Among responding patients with untreated AML, 74% had undetectable measurable residual disease (MRD), and 75% of responding patients with ts-AML had undetectable MRD. Patients with FLT3-ITD mutated AML who received sorafenib in addition to CLIA had a CR/CRi rate of 95%, with 81% negative for MRD. 

At a median follow-up of 76 months, patients with untreated AML had a 2- and 4-year overall survival of 57% and 50%, versus 20% and 13% in patients with ts-AML. The 2- and 5-year overall survival rates of patients treated with CLIA plus sorafenib were 63% and 59%, respectively. In terms of safety, the most common grade ≥3 adverse events included infection/fever, elevated bilirubin, rash, and nausea. 

Dr Kadia et al concluded, “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.” 

Source: 

Kadia TM, Ravandi F, Molica M, et al. Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia. Am J Hematol. Published online August 27, 2023. doi:10.1002/ajh.27054