背景:骨髓增生异常综合征(MDS)是孤儿,罕见疾病的发病率为4.6(US)/100,000;75%是低风险MDS(LR-MDS)。大约50%的LR-MDS患者发展为输血依赖性(TD)贫血,而与环铁皮母细胞(RS)状态无关。没有批准的RS-LR-MDS治疗方法。
目的:为了确定疾病负担,治疗模式,通过进行真实世界证据(RWE),以及ESA难治性或复发性(ESA-r/r)LR-MDS的成本,经济,和HRQoL系统文献综述(SLR)。
方法:按照PRISMA指南进行的SLR,补充会议记录(ASCO,EHA,ISPOR,ESMO,ASH)。
方法:ESA-r/r,TD,LR-MDS患者。
方法:ESA,HMA,来那度胺,Luspatercept,imetelstat,rigosertib.
方法:总生存期(OS),血液学改善(HI),输血独立性(TI),HRQoL,成本,住院治疗。
结果:9/28RWE研究纳入了ESA-r/r人群;两项研究报告与应答患者相比OS较低。6/28RWE研究包含TD人群;在三个中,与TI人群相比,TD患者的HI更差。没有RWE研究报告RS+,TD人口;然而,虽然RS状态不会影响TI,RS+人群的OS显著延长(2.8vs.2.1年,p<0.01;美国SEER医疗保险链接数据库)。5/14HRQoL研究发现TDLR-MDS受试者的HRQoL低于TI受试者(EQ-5D,FACT-An,EORTC-QLQ-C30)。MDS-CAN注册的证据表明,输血负担对RSLR-MDS的HRQoL产生负面影响。在MEDALIST审判中,ESA-r/r,RS+,LR-MDS患者的疾病负担较高(身体功能,角色功能,社会功能,疲劳,呼吸困难)相对于普通人群。RS+,与TI人群相比,TD人群的成本高3倍,住院风险增加(OR1.395%CI1.15-1.46),法国和加拿大的HRQoL较低。在这两项研究中,与输血相关的费用是LR-MDS经济负担的最大贡献者(美国,2008-2013;法国,2012-2013)。
结论:虽然TI在RWE中没有明确定义或普遍报告,ESA-r/r,TDLR-MDS人群(RS+/-)具有更差的结果,RS-状态显着降低生存率。在ESA-r/rLR-MDS中继续使用ESA和HMA表明存在高度未满足的需求。减少输血并改善RS状态耐久性的新疗法可能会改善HRQoL和结果。
背景:尼山·森古普塔,Geron公司。
BACKGROUND: Myelodysplastic syndromes (
MDS) are orphan, rare diseases with an incidence rate of 4.6 (US) per 100,000; 75% are low-risk
MDS (LR-
MDS). Approximately 50% of LR-MDS patients develop transfusion-dependent (TD) anemia irrespective of ring sideroblasts (RS) status. There are no approved treatments for RS-LR-
MDS.
OBJECTIVE: To identify the burden of illness, treatment patterns, and costs for ESA-refractory or relapsed (ESA-r/r) LR-MDS by conducting real-world evidence (RWE), economic, and HRQoL systematic literature reviews (SLRs).
METHODS: SLRs conducted following PRISMA guidelines, supplemented with conference proceedings (ASCO, EHA, ISPOR, ESMO, ASH).
METHODS: ESA-r/r, TD, LR-
MDS patients.
METHODS: ESAs, HMAs, lenalidomide, luspatercept, imetelstat, rigosertib.
METHODS: Overall survival (OS), hematological improvement (HI), transfusion independence (TI), HRQoL, costs, hospitalization.
RESULTS: 9/28 RWE studies included ESA-r/r populations; two studies reported lower OS compared with responding patients. 6/28 RWE studies contained a TD population; in three, HI was worse in TD patients compared to TI populations. No RWE studies reported an RS+, TD population; however, while RS status did not impact TI, OS was significantly longer in RS+ populations (2.8 vs. 2.1 years, p<0.01; US SEER Medicare-linked database). 5/14 HRQoL studies found TD LR-MDS subjects had lower HRQoL than TI subjects (EQ-5D, FACT-An, EORTC-QLQ-C30). Evidence from the MDS-CAN registry suggested that transfusion burden negatively affects HRQoL in RS+ LR-
MDS. In the MEDALIST trial, ESA-r/r, RS+, LR-MDS patients had a higher disease burden (physical functioning, role functioning, social functioning, fatigue, dyspnea) relative to the general population. RS+, TD populations are associated with 3-fold higher costs compared to TI populations, increased risk of hospitalization (OR 1.3 95% CI 1.15 - 1.46), and lower HRQoL in France and Canada. Transfusion-related costs were the largest contributor to the economic burden of LR-MDS in these two studies (US, 2008-2013; France, 2012-2013).
CONCLUSIONS: While TI is not well-defined or commonly reported in RWE, ESA-r/r, TD LR-MDS populations (RS+/-) have worse outcomes with RS- status significantly reducing survival. The continued use of ESAs and HMAs in ESA-r/r LR-MDS demonstrates a high unmet need. New therapies that reduce transfusions and improve durability across RS status may improve HRQoL and outcomes.
BACKGROUND: Nishan Sengupta, Geron Corporation.