Gilteritinib overcomes primary resistance to venetoclax in a patient with FLT3 wild-type refractory/relapsed AML: Case report and exploration of possible mechanisms

Man Li; Xiawan Yang; Yaonan Hong; Qi Liu; Yingying Shen; Tonglin Hu; Yiping Shen; Guoyin Kai; Dijiong Wu

doi:10.1016/j.heliyon.2024.e35847

Gilteritinib overcomes primary resistance to venetoclax in a patient with FLT3 wild-type refractory/relapsed AML: Case report and exploration of possible mechanisms

Heliyon. 2024 Aug 10;10(16):e35847. doi: 10.1016/j.heliyon.2024.e35847. eCollection 2024 Aug 30.

Authors

Man Li^{1

2}, Xiawan Yang^{2

3}, Yaonan Hong^{2

3}, Qi Liu^{2

3}, Yingying Shen^{2

3}, Tonglin Hu^{2

3}, Yiping Shen^{2

3}, Guoyin Kai¹, Dijiong Wu^{2

3

4}

Affiliations

¹ Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, Jinhua Academy, School of Pharmaceutical Sciences, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
² Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
³ The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
⁴ Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, China.

Abstract

Venetoclax, a selective BCL-2 inhibitor, has shown superior efficacy in the treatment of AML. Nevertheless, some AML patients with AML1-ETO respond poorly to venetoclax treatment. In this report, a relapsed/refractory (R/R) venetoclax resistant AML1-ETO positive AML patient showed rapid tumor regression after combination therapy with gilteritinib and venetoclax. Additional laboratory findings indicated that the combined impact of the two drugs may be associated with the induction of the integrated stress response. This case presents a novel therapeutic approach for the treatment of FLT3 wild-type RR, AML1-ETO AML patients who have primary resistance to venetoclax.

Keywords: Acute myeloid leukemia; Case report; Gilteritinib; Refractory/relapse; Venetoclax.

Publication types

Case Reports