Treatment Patterns and FLT3 Mutation Testing Among Patients with Acute Myeloid Leukemia in China: A Retrospective Observational Study

Abstract

Introduction

For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited.

Methods

In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020.

Results

Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3^MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time.

Conclusion

Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3^MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML.

Graphical Abstract

Keywords:

• acute myeloid leukemia
• epidemiology
• real-world
• retrospective study

Abbreviations

Allo-HSCT, allogeneic hematopoietic; AML, acute myeloid leukemia; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; FDA, US Food and Drug Administration; FLT3, FMS-like tyrosine kinase 3; FLT3-ITD, FMS-like tyrosine kinase 3 internal tandem duplication; FLT3^MUT, FMS-like tyrosine kinase 3 mutated; FLT3-TKD, FMS-like tyrosine kinase 3 tyrosine kinase domain; FLT3^WT, FMS-like tyrosine kinase 3 wild-type; IHBDH, Institute of Hematology and Blood Diseases Hospital; IQR, interquartile range; ND, newly diagnosed; NICHE, National Longitudinal Cohort of Hematologic Diseases; R/R, relapsed/refractory; SD, standard deviation.

Data Sharing Statement

Researchers may request access to anonymized participant-level data, trial-level data and protocols from Astellas-sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing see https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx.

Compliance with Ethics Guidelines

The study was conducted in accordance with the Declaration of Helsinki and International Conference of Harmonisation guidelines. The study was approved by the institutional review board committee of the IHBDH. The review board committee confirmed that informed consent was not needed from participants, and all data were anonymized prior to the current study.

Acknowledgments

The study was sponsored by Astellas Pharma Singapore Pte. Ltd. Medical writing support was provided by Rhian Harper Owen, PhD, from Lumanity, who assisted in drafting the manuscript under the direction of the authors and provided editorial support throughout its development. Editorial support was funded by Astellas Pharma, Inc.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Li-Jen Cheng and Prabhuram Krishnan are employees of Astellas Pharma Singapore Pte. Ltd. Christopher H. Young is an employee of Astellas Pharma US Inc. Jia Zhong and Eric Q. Wu are employees of Analysis Group, Inc., an HEOR CRO company contracted by Astellas to undertake analysis. Jianxiang Wang participated in an advisory board for AbbVie. The authors report no other conflicts of interest in this work.

Additional information

Funding

The study was sponsored by Astellas Pharma Singapore Pte. Ltd. Medical writing support and editorial support were funded by Astellas Pharma, Inc.