Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-dependent Anemia Due to Very Low-, Low- and Intermediate-risk (IPSS-R) Myelodysplastic Syndrome with Ring Sideroblasts: a Retrospective Multicenter Study by FISiM-ETS
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 215
- 试验地点
- 1
- 主要终点
- Transfusion independence for 8 weeks or longer during weeks 1 through 24
研究概览
简要总结
Myelodysplastic syndromes (MDS) are a group of malignancies characterized by reduced differentiation and increased apoptosis of hematopoietic progenitor cells, leading to ineffective hematopoiesis. Treatment of MDS varies according to prognosis. Patients with low IPSS-R risk have a low probability of progression to acute myeloid leukemia (AML) and the treatment is aimed at controlling cytopenia and improving quality of life (QOL). Anemia is the most common disease feature, occurring in 80%-85% of low-risk patients, 40% of whom eventually become RBC transfusion-dependent (TD).
Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta (TGF-beta) superfamily. Luspatercept binds to GDF11, GDF8, activin B, and other ligands. This binding leads to inhibition of Smad2/3 signaling, which is abnormally high in disease models of ineffective erythropoiesis such as MDS, resulting in erythroid maturation and differentiation.
Luspatercept is now approved for the treatment of adult patients with TD anemia due to very low-, low-, and intermediate-risk MDS with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.
FISiM (Fondazione Italiana Sindromi Mielodidplastiche) promotes a multicenter, retrospective observational study to collect information on the efficacy and safety of luspatercept in a real world Italian population of adult patients with transfusion-dependent anemia due to very low- and intermediate-risk MDS with ring sideroblasts
详细描述
Myelodysplastic syndromes (MDS) are a group of malignancies characterized by reduced differentiation and increased apoptosis of hematopoietic progenitor cells, leading to ineffective hematopoiesis. The incidence of MDS ranges from 1.5 to 4 cases per 100,000 individuals per year. Prognosis is determined by a number of factors, including age, cytogenetic abnormalities, and cytopenia as determined by the Revised International Prognostic Scoring System (IPSS-R), but also by the occurrence of molecular aberrations (eg, gene mutations) and red blood cell (RBC) transfusion dependence.
Treatment of MDS varies according to prognosis. Patients with low IPSS-R risk have a low probability of progression to acute myeloid leukemia (AML) and the treatment is aimed at controlling cytopenia and improving quality of life (QOL), whereas patients with high-risk disease have a shorter life expectancy and treatment is aimed at modifying the natural course of the disease.
Anemia is the most common disease feature, occurring in 80%-85% of low-risk patients, 40% of whom eventually become RBC transfusion-dependent (TD).
Besides lenalidomide, which is exclusively approved for patients with deletion of chromosome 5q, erythropoiesis-stimulating agents (ESAs) constitute the first option for patients with low risk disease. Patients who do not respond to ESAs have very limited options and ultimately require long-term RBC transfusions. Chronic transfusions lead to secondary iron overload and have a deleterious effect on the patient's QOL.
On April 26, 2019, Celgene Europe BV applied for a marketing authorization via the European Medicines Agency (EMA) centralized procedure for luspatercept (trade name Reblozyl). Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta (TGF-beta) superfamily. Luspatercept binds to GDF11, GDF8, activin B, and other ligands. This binding leads to inhibition of Smad2/3 signaling, which is abnormally high in disease models of ineffective erythropoiesis such as MDS, resulting in erythroid maturation and differentiation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (i.e. aged >=18 years) with diagnosis of MDS according to WHO 2016 classification that met IPSS-R criteria for very low, low, or intermediate-risk MDS along with the following additional criteria:
- •Ring Sideroblasts (RS) ≥15% of erythroid precursors in bone marrow in the absence of SF3B1 mutation, or ≥5% in the presence of SF3B1 mutation;
- •Bone marrow blasts <5%;
- •Peripheral white blood cell count <13,000/μL;
- •ECOG PS 0-2;
- •Refractory or intolerant to, or ineligible for prior ESA therapy.
- •Required RBC transfusions per the following criteria:
- •Mean RBC transfusion requirement ≥2 units/8 weeks in the 16 weeks before the start of luspatercept treatment
- •No consecutive 56-day period free from RBCTs in the 16 weeks before the start of luspatercept treatment
- •Treatment with luspatercept
排除标准
- •Any prior treatment with the following therapies:
- •Prior therapy with disease modifying agents for MDS including immunomodulatory drugs (eg, lenalidomide), hypomethylating agents (eg, azacitidine or decitabine), and immunosuppressive therapy.
- •Presence of the following conditions:
- •Pregnancy
- •The following blood and laboratory parameters: ANC <500/μL and Platelets <50,000/μL
研究组 & 干预措施
Luspatercept treated patients
Adult patients (i.e. aged >=18 years) with diagnosis of MDS according to WHO 2016 classification that met IPSS-R criteria for very low, low, or intermediate-risk MDS treated with Luspatercept
干预措施: Luspatercept (Drug)
结局指标
主要结局
Transfusion independence for 8 weeks or longer during weeks 1 through 24
时间窗: From week 1 through week 24 of treatment
Percentage of patients who achieved RBC Transfusion Independence (RBC-TI) ≥ 8 weeks from week 1 to week 24. RBC-TI response is defined as the absence of any RBC transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Patients had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 date to qualify as a responder. Patients who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders. Data will be summarised as frequencies and proportions or as medians and range and differences will be estimated by the chi square test (the Fisher exact test when appropriated) or the t test (the Wilcoxon Mann Whitney U test and the ANOVA model when appropriated based on patient characteristics distribution).
次要结局
- Transfusion independence for 12 weeks or longer, assessed during weeks 1 through 24(From Week 1 through Week 24 of treatment)
- Transfusion independence for 12 weeks or longer, assessed during weeks 1 through 48(From Week 1 through Week 48 of treatment)
- Transfusion independence for 8 weeks or longer from week 1 through week 48(From Week 1 through Week 48 of treatment)