Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study

To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P < 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).

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Journal
Blood Cancer Journal
Published
2024-12-18
DOI
https://doi.org/10.1038/s41408-024-01202-8
Citations
1
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.44

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article

Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study

Jie Jin, Wen Wu, Qingchi Liu, Guo‐Wei He et al.
1 citations
Blood Cancer Journal
Myeloproliferative Neoplasms: Diagnosis and Treatment
0.44
article

Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study

Jie Jin, Wen Wu, Qingchi Liu, Guo‐Wei He, Zhong‐Xing Jiang, Cheng‐Hao Jin, Binhua Lv, Zeping Zhou, Cuiping Zheng, Junling Zhuang, Mei Hong, Yan Li, Zhijian Xiao, Linhua Yang, Huanling Zhu, Shanshan Suo, Hewen Yin, Xin Du, Aili He, Yarong Li, Xin Li, Yi Zhang, Feng Zhang, Yuqing Chen, Qian Jiang, Hu Zhou, Jishi Wang, Yajing Xu, Lin Liu, Sujun Gao, Liqing Wu, Lingling Yue, Jin Zhang, Hongmei Jing, Dengshu Wu, Na Xu
article en
1 citations

Abstract

To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P < 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).

Blood Cancer JournalVol. 14(1)
Hebei Medical University (CN), Union Hospital (HK), Central South University (CN), Guiyang Medical University (CN), Shanxi Medical University (CN), Shanghai Jiao Tong University (CN), Jilin University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Kunming Medical University (CN), Peking Union Medical College Hospital (CN), Ruijin Hospital (CN), Sir Run Run Shaw Hospital (CN), Zhengzhou University (CN), West China Hospital of Sichuan University (CN), Wenzhou Central Hospital (CN), Nanfang Hospital (CN), Zhejiang Technical Institute of Economics (CN), Jiangxi Provincial People's Hospital (CN), Affiliated Hospital of Guizhou Medical University (CN), Lanzhou University Second Hospital (CN), Peking University People's Hospital (CN), First Hospital of Jilin University (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Second Affiliated Hospital of Xi'an Jiaotong University (CN), Henan Provincial People's Hospital (CN), Second Hospital of Shanxi Medical University (CN), First Hospital of China Medical University (CN), Peking University Third Hospital (CN), Second Affiliated Hospital of Jilin University (CN), Henan Cancer Hospital (CN), Guangdong Academy of Medical Sciences (CN), Shanghai Institute of Hematology (CN), Institute of Hematology & Blood Diseases Hospital (CN), First Affiliated Hospital of Bengbu Medical College (CN), Jiangsu Province Hospital (CN), Guangdong Provincial People's Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Third Xiangya Hospital (CN), First Affiliated Hospital of Hebei Medical University (CN), Xiangya Hospital Central South University (CN), First Affiliated Hospital Zhejiang University (CN), Huazhong University of Science and Technology (CN), Southern Medical University (CN), Zhejiang University (CN), Lanzhou University (CN), Nanjing Medical University (CN), Chongqing Medical University (CN), China Medical University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 29%
Myeloproliferative Neoplasms: Diagnosis and Treatment
0.44
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