Evaluation of treatment outcomes with CPX-351 in adults with AML: A meta-analysis.

Abstract

6540 Background: CPX-351 is a liposomal formulation of cytarabine and daunorubicin which has shown survival benefit when compared to 7+3 in older adults with myelodysplasia-related (AML-MRC) and therapy-related AML (t-AML). Aiming to investigate the clinical efficacy of CPX-351 against 7+3 in adults with AML, we performed a meta-analysis. Methods: A systematic search with controlled vocabulary encompassing AML, CPX-351 and 7+3 was conducted in PubMed, Embase, Scopus, and Cochrane on November 1, 2023 with no search restrictions. 3461 were found; 2581 were left after duplicates were removed using Mendeley 1.19.8. Remaining records were imported into Rayyan and independently screened by 2 reviewers. 8 studies were included in the analysis as they provided data for both CPX-351 and 7+3. 17 studies only including CPX-351 were identified. RevMan was used to analyze the Odds Ratio (OR) with 95% Confidence Interval (CI), derived from random effects (RE) model with Mantel-Haenszel (MH) method. Results: We identified 8 studies comparing CPX-351 to 7+3, encompassing a total of 1368 total patients: 44% (604/1368) received CPX-351, 56% (764/1368) received 7+3. Most patients had AML-MRC or t-AML. The median age in the CPX-351 group was 66 (range 58-67) and in the 7+3 group was 67 (range 58-67). The median overall survival grossly favored CPX-351 with 10.3 months (range 8.8-22 months) compared to 6.2 months (range 4.6-12 months) in 7+3. The OR of complete remission (CR) for CPX-351 versus 7+3 using the RE model was 1.66 (CI=1.15-2.39, p=0.006, I2=55%). Similarly, the OR of patients undergoing hematopoietic stem cell transplantation (HSCT) for CPX-351 versus 7+3 was 1.52 (CI=1.01-2.30, p=0.05, I2=47%). Including the additional 17 studies with CPX-351, the overall CR rate for all patients was 49%. Average 30-day mortality with CPX-351 was 4.9%. Conclusions: From our analysis, the OR of attaining CR and HSCT were shown to be significantly improved with CPX-351 when compared to conventional 7+3 chemotherapy in adult patients with AML. Both groups had similar median age, and patients in the CPX-351 arm had longer median overall survival. Our meta-analysis highlights that while CPX-351 achieves CR/HSCT at a higher rate than 7+3, data in younger populations (<60 years old) and patients with de novo AML are sparse. Heterogeneity between studies and lack of mutational analysis are limitations of our study. [Table: see text]