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. 2023 Sep;11(3):375-389.
doi: 10.1007/s40487-023-00239-2. Epub 2023 Aug 14.

French Retrospective Database Analysis of Patient Characteristics and Treatment Patterns in Patients with R/R FLT3-Mutated AML: A Registry-Based Cohort Study

Andy Garnham  1   2 , Franck Bruon  3 , Céline Berthon  4 , Delphine Lebon  5 , Mounika Parimi  6 , Rosalind Polya  6 , Kahina M Makhloufi  3 , Marie-Hélène Dramard-Goasdoue  3
Affiliations

French Retrospective Database Analysis of Patient Characteristics and Treatment Patterns in Patients with R/R FLT3-Mutated AML: A Registry-Based Cohort Study

Andy Garnham et al. Oncol Ther. 2023 Sep.

Abstract

Introduction: There is a dearth of evidence to document treatment of FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) in real-world settings before the introduction of FLT3 inhibitors. A retrospective cohort study was conducted to understand treatment practices prior to the availability of FLT3 inhibitors in patients with FLT3-mutated AML from two registries in France.

Methods: Patient data from January 1, 2009 to December 31, 2017 were collected from the Hauts-de-France and Midi-Pyrénées registries. Patients aged ≥ 18 years at diagnosis with FLT3-mutated AML were included. Demographic and disease characteristics of patients with FLT3-mutated AML and relapsed or refractory (R/R) FLT3-mutated AML were documented. Treatment regimens, overall survival (OS), and event-free survival were assessed in patients with R/R FLT3-mutated AML who did not participate in clinical trials.

Results: Overall, 819 and 1244 adult patients with AML from the Midi-Pyrénées and Hauts-de-France cohorts, respectively, underwent FLT3 mutation testing; 172 (21.0%) and 263 (21.1%) patients, respectively, had a FLT3 mutation. Primary R/R status was identified in 41.3% (n = 71/172) of the Midi-Pyrénées and 34.6% (n = 91/263) of the Hauts-de-France cohorts. Before R/R AML diagnosis, 82.0% and 97.5% of patients in the Midi-Pyrénées and Hauts-de-France cohorts, respectively, achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) following induction chemotherapy; after diagnosis of R/R AML, CR/CRi rates with salvage therapy were 33.3% and 28.1%, respectively. Median OS (interquartile range) in patients receiving salvage therapy (n = 49, n = 78) was 5.2 (2.3-11.1) and 6.1 (2.5-35.2) months, in the Midi-Pyrénées and Hauts-de-France cohorts, respectively. Across both cohorts, patients with R/R FLT3-mutated AML had low rates of CR/CRi with salvage therapy and a median OS of approximately 6 months.

Conclusion: Before FLT3 inhibitor availability, real-world treatment patterns and outcomes in French patients with R/R FLT3-mutated AML were consistent with clinical trial data, highlighting a poor prognosis and unmet need for effective treatment.

Keywords: FLT3 mutations; Real-world evidence; Relapsed or refractory acute myeloid leukemia; Treatment patterns.

Plain language summary

Acute myeloid leukemia is a cancer affecting the blood and bone marrow. The presence of specific mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in patients with acute myeloid leukemia can negatively impact response to standard chemotherapy. Patients with these mutations may not respond to chemotherapy or have a shortened duration of response causing a return of the disease, which in turn substantially decreases their life span. In the era prior to the availability of drugs specifically designed to counteract the negative effects of FLT3 mutations, evidence related to patient characteristics and treatment effects in individuals with acute myeloid leukemia harboring FLT3 mutations was mainly derived from clinical studies, with little evidence based on real-world experience. To better understand real-world patient characteristics and treatment effects in patients with acute myeloid leukemia and FLT3 mutations, we analyzed patients from two French registries, Midi-Pyrénées and Hauts-de-France, with a focus on patients who did not respond to or whose disease returned after initial chemotherapy. Patient data from between January 2009 and December 2017 included patients with FLT3-mutated acute myeloid leukemia from Midi-Pyrénées and Hauts-de-France who did not respond to or had recurrent disease after responding to initial chemotherapy, had low response to salvage chemotherapy, and a survival duration of 6 months or less. Our real-world observations in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia from these two registries were consistent with results reported in clinical trials. Our results highlight the bleak forecast for these patients in the absence of effective drugs.

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Conflict of interest statement

Andy Garnham, Franck Bruon, and Kahina M. Makhloufi are employees of Astellas Pharma. Marie-Hélène Dramard-Goasdoue was a former employee of Astellas, but they have since retired. Mounika Parimi and Rosalind Polya were employees of IQVIA during the data analysis of the study, which received funding from Astellas for the conduct of this study. Céline Berthon and Delphine Lebon have no conflicts to disclose.

Figures

Fig. 1
Fig. 1
Overall survival (OS) after the index date in the Midi-Pyrénées cohort. HSCT hematopoietic
Fig. 2
Fig. 2
Overall survival (OS) after the index date in the Hauts-de-France cohort. HSCT hematopoietic
Fig. 3
Fig. 3
Event-free survival (EFS) after the index date in the Midi-Pyrénées cohort
See this image and copyright information in PMC

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