Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia

Abstract

CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.

Graphical abstract

Figure 1.

Patient flow diagram. MDS EB, myelodysplastic syndrome with excess blasts.

Figure 2.

OS and subgroup survival. (A) OS according to treatment arm (n = 656). HR and 95% CI are shown. (B) Selected univariate subset analyses for comparison of CPX-351 vs ven/aza.

Figure 3.

Survival with restriction to CPX-351 trial-eligible patients and across sensitivity analyses. (A) OS with population restricted to 60 to 75 year olds with a history of a therapy-related myeloid neoplasm, myelodysplasia-related cytogenetics, or history of MDS (n = 267). (B) Plot of HR for OS for CPX-351 vs ven/aza across multiple analyses including unadjusted univariate Cox analysis, multivariate Cox analysis, univariate Cox analysis after multiple imputation, multivariate Cox regression analysis after multiple imputation, and Cox regression analysis after multiple imputation with inverse probability of treatment weighting.