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
Affiliations
Man Li
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; Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
Xiawan Yang
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Yaonan Hong
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Qi Liu
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Yingying Shen
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Tonglin Hu
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Yiping Shen
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Guoyin Kai
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; Corresponding author. author. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
Dijiong Wu
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China; The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, China; Corresponding author. Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China.
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.
