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3165 Post Hoc Analysis of Phase III Gecacitinib Clinical Trial Outcomes: Enhanced Understanding and Implications

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, MPN, Clinical Research, Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Yi Zhang1*, Hu Zhou2, Shanshan Suo, MD1*, Junling Zhuang, MD, PhD3, Linhua Yang, MD4*, Aili He, PhD, MD5*, Qingchi Liu6*, Xin Du, PhD7, Sujun Gao8*, Yarong Li9*, Yan Li10*, Yuqing Chen11*, Wen Wu12*, Huanling Zhu13*, Guangsheng He14*, Mei Hong, MD15*, Qian Jiang, MD16, Zhongxing Jiang17*, Hongmei Jing18, Jishi Wang, PhD19, Na Xu20*, Lingling Yue21*, Cuiping Zheng22*, ZePing Zhou, MD, PhD23, Chenghao Jin24*, Xin Li25*, Lin Liu26*, Yajing Xu, MD27*, Dengshu Wu28*, Feng Zhang29*, Jin Zhang30*, Zhijian Xiao, MD31* and Jie Jin, M.D.32

1Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2Department of Hematology, Henan Provincial Cancer Hospital, Zhengzhou, China
3Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
4The Second Hospital of Shanxi Medical University, Taiyuan, China
5Department of Hematology, The Second Affiliated Hospital of Xi’an Jiao Tong University, Xi'an Key Laboratory of Hematological Diseases, Xi’an, China
6The First Hospital of Hebei Medical University, Shijiazhuang, China
7Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, WA, China
8Department of Hematology, The First Hospital of Jilin University, Changchun, China
9Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, CHN
10Department of Hematopathology, The First Affiliated Hospital of China Medical University, Shenyang, China
11Department of Hematology, Henan Province People's Hospital, Zhengzhou, China
12Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
13Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
14The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Key Laboratory of Hematology of Nanjing Medical University, Collaborative Innovation Center for Cancer Personalize, Nanjing, China
15Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
16National Clinical Research Center for Hematologic Disease, Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, Beijing, China
17The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
18Peking University Third Hospital, Beijing, CHN
19Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang City, China
20Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
21Department of Hematology and Oncology, Lanzhou University Second Hospital, Lanzhou, China
22Second Department of Oncology, Wenzhou Central Hospital, Wenzhou, China
23Second Affiliated Hospital of Kunming Medical University, Kunming, China
24Jiangxi Provincial People's Hospital, Nanchang, China
25Department of Hematology, Third Xiangya Hospital of Central South University, Changsha, China
26Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
27Xiangya Hospital, Central South University, Changsha, Hunan, China
28Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
29Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
30Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
31MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
32Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Background: Myelofibrosis clinical manifestations typically include significant splenomegaly, high symptom burden and severe anemia. A phase III study (ZGJAK016) of gecacitinib (also known as jaktinib) met its primary endpoint, demonstrating 64.8% patients with a spleen volume reduction of ≥35% from baseline at week 24, along with favorable benefits in symptoms and anemia (presented at the European Hematology Association Hybrid Congress 2024). Herein, we present additional efficacy data that complement the positive findings from the ZGJAK016 study.

Methods: A total of 105 myelofibrosis patients were included in the study (71 patients were randomized to gecacitinib and 34 to hydroxyurea). Key endpoints included changes in spleen length assessed by palpation, individual symptom score improvements, and transfusion independence rate. Transfusion independence was defined as not requiring red blood cell transfusion (except in cases of clinically overt bleeding) for ≥12 weeks, with hemoglobin ≥80 g/L.

Results: Baseline characteristics were similar between treatment groups. The median spleen lengths were 15.0 cm and 13.3 cm in the gecacitinib and hydroxyurea groups. The median total symptom scores were 20.0 points and 19.0 points, respectively. A total of 77 (73.3%) symptomatic patients had a baseline total symptom score of ≥10 points (50 [70.4%] in the gecacitinib group and 27 [79.4%] in the hydroxyurea group). A lower proportion of patients in the gecacitinib group were transfusion-independent at baseline compared to hydroxyurea (70.4% vs. 76.5%).

At Week 2, mean percentage changes from baseline in spleen length were -25.1% and -6.4% in the gecacitinib and hydroxyurea groups, with a higher proportion of patients achieving in a ≥50% decrease in palpable spleen length in the gecacitinib than in the hydroxyurea group (17.4% vs. 0, respectively).

84.5% for gecacitinib and 61.8% for hydroxyurea achieved a ≥50% total symptom score reduction from baseline at any time (p = 0.0109). At Week 24, significant symptom improvement was observed in the gecacitinib group for each individual item, with mean percentage changes from baseline exceeding 50% in almost all cases (fatigue: -52.5%; early satiety: -59.7%; abdominal discomfort: -62%; inactivity: -39.6%; problems with concentration: -44.7%; night sweats: -87.7%; fever: -59.8%; weight loss: -87.6%; itching: -65.1%; and bone pain: -50.6%). In the symptomatic population, patients treated with gecacitinib showed higher rates of symptom improvement—defined as a decrease of at least 2 points—compared to those who received hydroxyurea in most individual items. This was particularly notable in night sweats (69.4% vs. 38.5%).

Transfusion independence rates at Week 24 were achieved by 60.6% of 71 patients in the gecacitinib group and 38.2% of 34 in the hydroxyurea group, with a rate difference of 22.8% (95% CI, 3.1% to 42.5%; p = 0.0288). A steady increase in mean hemoglobin levels over time has been observed in patients with a baseline level of less than 100 g/L.

Conclusions: The findings indicate that gecacitinib not only reaffirms its high efficacy in splenic size reduction but also demonstrates a rapid onset of action. In terms of symptom improvement, it significantly alleviated a range of symptoms, particularly in symptomatic patients. Regarding anemia, gecacitinib enhanced transfusion independence as evidenced by a higher transfusion independence rate at Week 24 compared to hydroxyurea, with comparable baseline characteristics. The ZGJAK016 study validates the critical role of gecacitinib in addressing the core treatment needs of myelofibrosis patients.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH