Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses

Abstract

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 7+3 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 7+3. 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 7+3 (52/56 [33%]) on outcomes. CPX-351 improved median OS vs 7+3 in patients who achieved CR or CRi (25.43 vs 10.41 months; hazard ratio = 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 = 0.43; 95% confidence interval, 0.21, 0.89), and a safety profile that was consistent with the known safety profile of 7+3. 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.

Conflict of interest statement

Conflict-of-interest disclosure: D.A.R. served as a consultant for AbbVie, Novartis, Pfizer, Spectrum, and Teva; and served on speakers bureaus for Gilead, Incyte, Jazz Pharmaceuticals, Millennium, and Seattle Genetics. D.H.R. holds stock ownership in AbbVie and patents/royalties with the University of Rochester. G.J.S. received research funding from AbbVie, Agios, Actinium, Amgen, Ariad, Astellas Pharma, Bristol Myers Squibb, Constellation, Cyclacel, Daiichi Sankyo, Deciphera, Delta-Fly, Forma, Fujifilm, Gamida, Genentech-Roche, Geron, Incyte, Jazz Pharmaceuticals, Karyopharm, Kite Pharma, Mateon, MedImmune, Novartis, Onconova, Pfizer, REGiMMUNE, Samus, Sangamo, Tolero, and Trovagene; served as a consultant for Agios, Amgen, AstraZeneca, Incyte, Novartis, and Ono Pharma; served on speakers bureaus for Agios, Amgen, Celgene, Gilead, Incyte, Sanofi, and Stemline; provided expert testimony for Kaiser Permanente; and holds stock in Amgen, Bristol Myers Squibb, Johnson & Johnson, and Pfizer. J.E.K. received honoraria from Gilead, Magellan, and Novartis; served as a consultant for Gilead, Magellan, Novartis, Pharmacyclics, and Seattle Genetics; received research funding from Boehringer Ingelheim, Cantex, Erytech, and Millennium; and received travel support from Gilead, Novartis, and Seattle Genetics. G.L.U. served as a consultant for Jazz Pharmaceuticals and Genentech and received honoraria from Astellas Pharma. M.J.W. received research funding from Amgen, Leadiant, Merck, and Shire; participated in advisory committees for Daiichi Sankyo; and holds stock ownership in Reata Pharmaceuticals. R.J.R. and S.F. are employees of and hold stock ownership/options in Jazz Pharmaceuticals. J.E.C. served as a consultant for Astellas Pharma, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, and Pfizer; and received research funding from Arog, Astellas Pharma, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, and Pfizer. J.E.L. served as a consultant for Agios, Daiichi Sankyo, Jazz Pharmaceuticals, and Pfizer. The remaining authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

OS in patients who achieved CR or CRi. Among patients who achieved CR or CRi, median OS was numerically longer with CPX-351 vs 7+3 overall (A) and generally across the evaluated subgroups of patients (B-G). KM, Kaplan-Meier; NE, not estimable.

Figure 2.

OS landmarked from the HCT date in patients who achieved CR or CRi. Among patients who achieved CR or CRi and subsequently underwent HCT, median OS landmarked from the HCT date was numerically longer with CPX-351 vs 7+3 overall (A) and across the evaluated subgroups of patients (B-F).