Consolidation outcomes in CPX-351 versus cytarabine/daunorubicin-treated older patients with high-risk/secondary acute myeloid leukemia

Abstract

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60–75 years with newly diagnosed, high-risk/secondary AML received 1–2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25–0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%–61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients.

Keywords:

• CPX-351
• consolidation
• daunorubicin
• cytarabine
• acute myeloid leukemia

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 William Perlman, PhD, and Kimberly Brooks, PhD, CMPP, of SciFluent Communications under the direction of the authors and were financially supported by Jazz Pharmaceuticals.

Disclosure statement

J Kolitz has received honoraria from Gilead, Magellan, and Novartis; consulting fees from Gilead, Magellan, Novartis, Pharmacyclics, and Seattle Genetics; institutional research funding from Boehringer Ingelheim, Cantex, Erytech, and Millennium; and travel support from Gilead, Novartis, and Seattle Genetics. S Strickland has received consulting fees from Astellas, Baxalta, Boehringer Ingelheim, CTI BioPharma, Daiichi-Sankyo, Sunesis, and Tolero; and institutional research funding from Boehringer Ingelheim and Sunesis. J Cortes has received consulting fees from Amphivena, Ariad, BiolineRX, Bristol-Myers Squibb, Janssen, Novartis, and Pfizer; and institutional research funding from Ambit, Araid, Arog, Astellas, Bristol-Myers Squibb, Celgene, ImmunoGen, Incyte, Jazz Pharmaceuticals, Novartis, Pfizer, and Teva. D Hogge has received consulting fees from Novartis, Roche, and Sanofi. J Lancet has received consulting fees from Biopath, Biosight, Boehringer Ingelheim, Jazz Pharmaceuticals, Celgene, Janssen, Karyopharm, and Novartis; and institutional research funding from Pfizer. S Goldberg has received consulting fees from Bristol-Myers Squibb and Novartis; participated in spearkers’ bureaus for Ariad, Bristol-Myers Squibb, Celgene, and Novartis; received institutional research funding from Ambit, Astellas, Bristol-Meyers Squibb, Celgene, Jazz Pharmaceuticals, Novartis, and Pfizer; provided expert testimony for Novartis; and is an employee of and holds stock ownership in COTA. K Villa, M Chiarella, and A Louie are former employees of and hold stock ownership in Jazz Pharmaceuticals; A Louie additionally holds patents/royalties with Jazz Pharmaceuticals. R Ryan is an employee of and holds stock ownership in Jazz Pharmaceuticals. E Ritchie has received consulting fees from Incyte, Celgene, Pfizer, and Novartis; research funding from Pfizer, Novartis, Astellas Pharma, Bristol-Myers Squibb, and NS Pharma; has participated in speakers’ bureaus for Incyte, Celgene, Novartis, and ARIAD Pharmaceuticals; and received travel support from Celgene and Novartis. R Stuart has received research funding from Sunesis Pharmaceuticals, Agios, Astellas Pharma, Bayer AG, Jazz Pharmaceuticals, and Incyte; and travel support, honoraria, and consulting fees from Sunesis Pharmaceuticals.

Data availability statement

All relevant data are provided within the manuscript and supporting files. The study protocol and statistical analysis plan are available as online supplemental content for Lancet JE, et al. JCO. 2018;36(26):2684-2692.

Additional information

Funding

This study was funded by Jazz Pharmaceuticals, Inc.