CPX-351 vs FLAG-Ida Treatment for Patients With Adverse Karyotype AML/High-Risk MDS

The UK NCRI AML19 trial

The overall survival of younger patients with adverse risk acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) was not significantly different between those treated with liposomal daunorubicin and cytarabine (CPX-351) and those treated with standard-of-care regimen of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida), according to findings from the UK NCRI AML19 trial. 

“Liposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients with secondary acute myeloid leukemia (AML),” explained Jad Othman, MD, Kings College London, United Kingdom, adding “to date, there have been no randomized studies in younger patients.” 

A total of 189 patients of a median age of 56 years were randomized to receive either CPX-351 or FLAG-Ida. Of this group, 49% of patients had de novo AML, 20% had secondary AML, and 30% had high-risk MDS. MDS-related cytogenetics were present in 73% of the patients, with a complex karyotype in 49%. Study authors noted that TP53 was the most commonly mutated gene in 43% of patients, while myelodysplasia-related gene mutations were present in 44% of patients.

The overall response rate, calculated by complete remission (CR) plus complete remission CR with incomplete blood count recovery (CRi) after course 2 was 64% and 76% for CPX-351 and FLAG-Ida, respectively. There was no difference in OS (13.3 months vs 11.4 months) or event-free survival, as assessed by multivariable analysis. However, relapse-free survival was significantly longer with CPX-351, at a median of 22.1 vs 8.35 months. 

Overall, the study authors found no difference between the treatment arms in patients with clinically defined secondary AML or those with MDS-related cytogenetic abnormalities. They noted that an exploratory subgroup of patients with MDS-related gene mutations had significantly longer OS with CPX-351, at a median of 38.4 vs 16.3 months. 

“In this randomized comparison between FLAG-Ida and CPX-351 in younger adults with newly diagnosed AML and high-risk MDS with an adverse karyotype, there was no detectable difference in OS between treatments,” Othman and coauthors concluded. 

Source:

Othman J, Wilhelm-Benartzi C, Dillon E, et al. A randomized comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS. Blood Advances. Published online August 11, 2023. doi: 10.1182/bloodadvances.2023010276