Early mortality and overall survival in acute promyelocytic leukemia: do real-world data match results of the clinical trials?

Abstract

Acute promyelocytic leukemia (APL) boasts overall survival (OS) of >90% at 3 years and early mortality of <5% in recent clinical trials. Using a large National Cancer Database, we performed analysis of 7190 adults with APL to determine whether one-month mortality and OS of patients with APL treated in real-world practices mirror outcomes noted in clinical trials. Only 64% of total patients received multi-agent therapy; 32% received either single-agent therapy or no therapy at all. One-month mortality was 6% for patients ≤18 years, 6% for 19–40 years, 10% for 41–60 years, and 21% for >60 years. OS at 1- and 3-year were 81% and 75%, respectively. In a multivariate analysis, age ≤ 40 years, treatment at academic center, use of multi-agent therapy, and diagnosis after 2009 conferred better OS. In this largest database study in APL till date, we demonstrated an overall improvement in OS over time but challenges still exist in translating successes of clinical trials to real-world practices.

Keywords:

• Acute promyelocytic leukemia
• one-month mortality
• overall survival
• leukemia
• older adults
• clinical trials

Acknowledgements

The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used in the study are derived from a deidentified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology used or the conclusions drawn from these data by the investigators. Amer Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and was also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

Vijaya Bhatt reports receiving consulting fees from Takeda, Omeros, Agios, Abbvie, Genentech, Partner therapeutics, Rigel, Incyte and Partnership for health analytic research, LLC (which receives funds from Jazz), and research funding (institutional) from Jazz, Abbvie, Pfizer, Incyte, Tolero Pharmaceuticals, Inc, and National Marrow Donor Program. Drug support for a trial is provided by Oncoceutics. Krishna Gundabolu reports serving as a consultant for Jazz Pharmaceuticals, Pfizer, and Novartis. Chakra Chaulagain reports receiving honoraria from Sanofi Genzyme. Amer M. Zeidan received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene/Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Geron, and Celgene/BMS. AMZ received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. None of these relationships were related to the development of this manuscript. There are no conflicts of interest for any other authors.

Additional information

Funding

This work was supported by the National Institute of General Medical Sciences, 1 U54 GM115458, which funds the Great Plains Institutional Development Award (IDeA) Clinical Translational Research (CTR) Network.