Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy.

Acute myeloid leukemia Azacitidine Measurable residual disease Predictive factor Venetoclax WT1 mRNA

Journal

International journal of clinical oncology
ISSN: 1437-7772
Titre abrégé: Int J Clin Oncol
Pays: Japan
ID NLM: 9616295

Informations de publication

Date de publication:
09 Feb 2024
Historique:
received: 27 09 2023
accepted: 14 01 2024
medline: 9 2 2024
pubmed: 9 2 2024
entrez: 9 2 2024
Statut: aheadofprint

Résumé

Wilms' tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported. This study aims to elucidate whether WT1 mRNA dynamics could predict long-term prognosis. 33 patients with untreated or relapsed/refractory AML evaluated for peripheral blood WT1 dynamics in VEN combination therapy were analyzed. The median age was 73 years (range 39-87). Azacitidine was combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210-482), and the complete remission (CR) plus CR with incomplete hematologic recovery rate was 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment was associated with significantly better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, p = 0.049; median EFS 270 days vs. 125 days, p = 0.02). The negativity of post-treatment WT1 mRNA value during the treatment was associated with significantly better OS and EFS (median OS 482 days vs. 256 days, p = 0.02; median EFS not reached vs. 150 days, p = 0.005). Multivariate analysis confirmed the significance of these two parameters as strong EFS predictors (HR 0.26, p = 0.024 and HR 0.15, p = 0.013, respectively). The increase in WT1 mRNA values was correlated with relapse. This study demonstrates that WT1 mRNA dynamics can be a useful marker for assessing long-term prognosis of VEN combination therapy for AML.

Sections du résumé

BACKGROUND BACKGROUND
Wilms' tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported. This study aims to elucidate whether WT1 mRNA dynamics could predict long-term prognosis.
METHODS METHODS
33 patients with untreated or relapsed/refractory AML evaluated for peripheral blood WT1 dynamics in VEN combination therapy were analyzed.
RESULTS RESULTS
The median age was 73 years (range 39-87). Azacitidine was combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210-482), and the complete remission (CR) plus CR with incomplete hematologic recovery rate was 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment was associated with significantly better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, p = 0.049; median EFS 270 days vs. 125 days, p = 0.02). The negativity of post-treatment WT1 mRNA value during the treatment was associated with significantly better OS and EFS (median OS 482 days vs. 256 days, p = 0.02; median EFS not reached vs. 150 days, p = 0.005). Multivariate analysis confirmed the significance of these two parameters as strong EFS predictors (HR 0.26, p = 0.024 and HR 0.15, p = 0.013, respectively). The increase in WT1 mRNA values was correlated with relapse.
CONCLUSION CONCLUSIONS
This study demonstrates that WT1 mRNA dynamics can be a useful marker for assessing long-term prognosis of VEN combination therapy for AML.

Identifiants

pubmed: 38334897
doi: 10.1007/s10147-024-02480-9
pii: 10.1007/s10147-024-02480-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

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Auteurs

Honami Sato (H)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Takahiro Kobayashi (T)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. takahiro@med.akita-u.ac.jp.

Yoshihiro Kameoka (Y)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Kazuaki Teshima (K)

Department of Hematology, Hiraka General Hospital, Yokote, Japan.

Atsushi Watanabe (A)

Department of Hematology, Nephrology and Rheumatology, Omagari Kousei Medical Center, Daisen, Japan.
Department of Hematology, Akita City Hospital, Akita, Japan.

Masahiro Yamada (M)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Department of Hematology, Hiraka General Hospital, Yokote, Japan.
Department of Hematology, Nephrology and Rheumatology, Omagari Kousei Medical Center, Daisen, Japan.

Takaya Yamashita (T)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Shinsuke Noguchi (S)

Department of Hematology, Akita Red Cross Hospital, Akita, Japan.

Yoshihiro Michisita (Y)

Department of Hematology, Akita Kousei Medical Center, Akita, Japan.

Naohito Fujishima (N)

Department of Hematology, Nephrology and Rheumatology, Nohsiro Kousei Medical Center, Noshiro, Japan.

Jun Kuroki (J)

Department of Internal Medicine, Yuri Kumiai General Hospital, Yurihonjo, Japan.

Naoto Takahashi (N)

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Classifications MeSH