Hetrombopag for Low/Intermediate-1 Risk MDS With Thrombocytopenia

Myelodysplastic syndrome (MDS) is a kind of clonal myeloid tumor. The major manifestation is decrease of tri-lineages of blood due to ineffective and abnormal hematopoiesis, some of which can progress to acute myeloid leukemia. According to the international prognosis scoring system (IPSS) of MDS, about 10% low/intermediate risk-1 MDS patients have severe thrombocytopenia (PLT < 30 × 109/ L). These patients have both decreased platelet count and platelet dysfunction, resulting in a high risk of bleeding. In the new prognostic score, such as IPSS-r, the degree of thrombocytopenia is regarded as a poor prognostic factor. Platelet transfusion is mainly used in the treatment of this kind of patients. The indications of transfusion include bleeding events or severe platelet count reduction (< 10 × 109 / L). However, platelet transfusion can only lead to short-term platelet elevation, while repeated transfusion increases the possibility of infection and ineffective platelet transfusion. TPO is a newly discovered hematopoietic promoting factor, which can specifically bind to the TPO receptor on the cell and participate in the regulation of proliferation, differentiation, maturation and division of megakaryocyte to form functional platelet. The efficacy and safety of the TPO receptor agonists eltrombopag and romiplostim in the treatment of thrombocytopenia in low/intermediate risk-1 MDS patients have been successfully confirmed in foreign studies. Hetrombopag is a new kind of a TPO receptor agonists which is highly specific platelet stimulating factor. At present, there is no large report on the application of Hetrombopag in such patients. The purpose of this study is to explore the short-term and long-term therapeutic effect and safety of Hetrombopag on low/intermediate risk-1 MDS patients.

stanozolol 2mg tid + Hetrombopag (started with 5mg/day and increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L, the maximum dosage is 15mg/day)

Hetrombopag would be given started with 5mg/day and increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L, the maximum dosage is 15mg/day)

Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at 6 months

percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 12 months

to evaluate the severity of bleeding, the proposed normal cutoffs are >=4 in adult males, >=6 in adult females, and >=3 in children, respectively

life quality for MDS patients by QoL-E questionaire（scores range from 0 to 100，higher scores mean better).

Inclusion Criteria: Confirmed MDS, IPSS low / intermediate risk-1 In the 4 weeks before inclusion, the average value of platelets was ≤ 30 × 10e9 / L, or < 50 × 10e9 / L with bleeding events Patients with EPO due to anemia and G-CSF due to severe neutropenia can be included, and the dosage will not change during trial ECOG 0-2 points Able to sign informed consent Exclusion Criteria: Pregnant or lactating IPSS intermediate risk-2 / high risk MDS More than 5% of myeloblasts in bone marrow Myelofibrosis Previous transplantation or ATG treatment within 6 months Previous use of TPO or other TPO receptor agonists Active infection or tumor Thromboembolic or hemorrhagic disease Serious heart disease, including unstable angina, congestive heart failure, arrhythmia, 1-year history of myocardial infarction Baseline liver and kidney function: ALT / ASL over than 3 times normal upper limit, TBIL over than 2 times normal upper limit, and creatinine over than 2 times normal upper limit

Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, Hou M, Yao Y, Liu L, Wang Y, Wu D, Zhang L, Zheng C, Shen X, Hu Q, Liu J, Jin J, Luo J, Zeng Y, Gao S, Zhang X, Zhou X, Shi Q, Xia R, Xie X, Jiang Z, Gao L, Bai Y, Li Y, Xiong J, Li R, Zou J, Niu T, Yang R, Hu Y. A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9.