Abstract
To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10−3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.
Highlights
Acute myeloid leukemia (AML) can arise de novo, as therapyrelated complication following chemotherapy and/or ionizing radiation (t-AML) or from antecedent hematologic disorders [1]
SUBJECTS AND METHODS Study design For this retrospective analysis, we collected data from consecutive patients with newly diagnosed AML with myelodysplasia-related changes (AML-MRC) or t-AML, who were treated with CPX-351 according to the EMA label between 2018 and 2020 in 25 German centers participating in the Study Alliance Leukemia (SAL), German Cooperative Transplant Study Group, and the AML Study Group (AMLSG)
Our results show that in a real-life setting CPX-351 is used in patients exhibiting high-risk characteristics, which are in many aspects comparable to those in the phase-III trial, and to those reported in two other real-world data sets of 103 and 71 patients [6, 10, 11]
Summary
Acute myeloid leukemia (AML) can arise de novo, as therapyrelated complication following chemotherapy and/or ionizing radiation (t-AML) or from antecedent hematologic disorders [1]. While attempts to improve outcome after induction therapy by addition of other agents or intensification of post-remission therapy have generally failed, higher remission rates and longer overall survival (OS) compared to conventional cytarabine plus daunorubicin chemotherapy (7 + 3 regimen) were recently observed following CPX-351 (Jazz Pharmaceuticals, Palo Alto, CA), a liposomal encapsulation of cytarabine and daunorubicin at a fixed 5:1 synergistic molar ratio [6, 7] The results from this phase-III trial, which investigated CPX-351 in 309 patients with between allo-HCT and death or date of last follow-up in surviving patients, while relapse-free survival (RFS) was calculated as time from allo-HCT until relapse or death without relapse censoring those patients, who had not relapsed until and were alive at date of last follow-up. Time-to-event curves were calculated by employing the Kaplan–Meier method and logrank tests were applied for univariate comparisons
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
