TY - JOUR
T1 - Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351
T2 - Phase 3 post hoc analyses
AU - Lin, Tara L.
AU - Rizzieri, David A.
AU - Ryan, Daniel H.
AU - Schiller, Gary J.
AU - Kolitz, Jonathan E.
AU - Uy, Geoffrey L.
AU - Hogge, Donna E.
AU - Solomon, Scott R.
AU - Wieduwilt, Matthew J.
AU - Ryan, Robert J.
AU - Faderl, Stefan
AU - Cortes, Jorge E.
AU - Lancet, Jeffrey E.
N1 - Funding Information:
Acknowledgments The authors thank all of the patients who participated in the study and their families, as well as the investigators, nurses, coordinators, and other research staff at each study site. Medical writing and editorial support were provided by Senem Kurtoglu Lubin, of SciFluent Communications, Inc, under the direction of the authors and were financially supported by Jazz Pharmaceuticals. This study was supported by Jazz Pharmaceuticals.
Publisher Copyright:
© 2021 by The American Society of Hematology
PY - 2021/3/23
Y1 - 2021/3/23
N2 - CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 713 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 713. These exploratory post hoc subgroup analyses evaluated the impact of achieving complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) with CPX-351 (73/153 [48%]) vs conventional 713 (52/56 [33%]) on outcomes. CPX-351 improved median OS vs 713 in patients who achieved CR or CRi (25.43 vs 10.41 months; hazard ratio 5 0.49; 95% confidence interval, 0.31, 0.77). Improved median OS was seen across AML subtypes (t-AML, AML-MRC), age subgroups (60 to 69 vs 70 to 75 years), patients with prior hypomethylating agent exposure, and patients who did not undergo transplantation. Patients who achieved CR or CRi with CPX-351 also had a higher rate of transplantation, a longer median OS landmarked from the date of transplantation (not reached vs 11.65 months; hazard ratio 5 0.43; 95% confidence interval, 0.21, 0.89), and a safety profile that was consistent with the known safety profile of 713. These results suggest deeper remissions may be achieved with CPX-351, leading to improved OS. This study was registered at www.clinicaltrials.gov as #NCT01696084.
AB - CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 713 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 713. These exploratory post hoc subgroup analyses evaluated the impact of achieving complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) with CPX-351 (73/153 [48%]) vs conventional 713 (52/56 [33%]) on outcomes. CPX-351 improved median OS vs 713 in patients who achieved CR or CRi (25.43 vs 10.41 months; hazard ratio 5 0.49; 95% confidence interval, 0.31, 0.77). Improved median OS was seen across AML subtypes (t-AML, AML-MRC), age subgroups (60 to 69 vs 70 to 75 years), patients with prior hypomethylating agent exposure, and patients who did not undergo transplantation. Patients who achieved CR or CRi with CPX-351 also had a higher rate of transplantation, a longer median OS landmarked from the date of transplantation (not reached vs 11.65 months; hazard ratio 5 0.43; 95% confidence interval, 0.21, 0.89), and a safety profile that was consistent with the known safety profile of 713. These results suggest deeper remissions may be achieved with CPX-351, leading to improved OS. This study was registered at www.clinicaltrials.gov as #NCT01696084.
UR - http://www.scopus.com/inward/record.url?scp=85103212679&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2020003510
DO - 10.1182/bloodadvances.2020003510
M3 - Article
C2 - 33724305
AN - SCOPUS:85103212679
SN - 2473-9529
VL - 5
SP - 1719
EP - 1728
JO - Blood advances
JF - Blood advances
IS - 6
ER -