小狗阅读会员会员
有解析的医学SCI阅读工具

扫码登录小狗阅读

阅读SCI医学文献

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study.

卡非佐米、地塞米松和达雷妥尤单抗与卡非佐米和地塞米松治疗复发性或难治性多发性骨髓瘤患者 (CANDOR): 一项随机、多中心、开放标签、3期研究的结果。

  • 影响因子:10.28
  • DOI:10.1016/S0140-6736(20)30734-0
  • 作者列表:"Dimopoulos M","Quach H","Mateos MV","Landgren O","Leleu X","Siegel D","Weisel K","Yang H","Klippel Z","Zahlten-Kumeli A","Usmani SZ
  • 发表时间:2020-07-18
Abstract

BACKGROUND:Lenalidomide and bortezomib frontline exposure has raised a growing need for novel treatments for patients with relapsed or refractory multiple myeloma. Carfilzomib in combination with daratumumab has shown substantial efficacy with tolerable safety in relapsed or refractory multiple myeloma in a phase 1 study. In this study, we aimed to compare the efficacy and safety of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. METHODS:In this randomised, multicentre, open-label, phase 3 study, 466 patients recruited from 102 sites across North America, Europe, Australia, and Asia with relapsed or refractory multiple myeloma were randomly assigned 2:1 to carfilzomib, dexamethasone, and daratumumab (KdD) or carfilzomib and dexamethasone (Kd). All patients received twice per week carfilzomib at 56 mg/m2 (20 mg/m2; days 1 and 2 during cycle 1). Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3-6), and every 4 weeks thereafter. Patients received 40 mg dexamethasone weekly (20 mg for patients ≥75 years old starting on the second week). The primary endpoint was progression-free survival assessed by intention to treat. Adverse events were assessed in the safety population. This trial (NCT03158688) is registered with ClinicalTrials.gov, and is active but not recruiting. FINDINGS:Between June 13, 2017, and June 25, 2018, 466 patients of 569 assessed for eligibility were enrolled. After median follow-up of approximately 17 months, median progression-free survival was not reached in the KdD group versus 15·8 months in the Kd group (hazard ratio 0·63; 95% CI 0·46-0·85; p=0·0027). Median treatment duration was longer in the KdD versus the Kd group (70·1 vs 40·3 weeks). Grade 3 or higher adverse events were reported in 253 (82%) patients in the KdD group and 113 (74%) patients in the Kd group. The frequency of adverse events leading to treatment discontinuation was similar in both groups (KdD, 69 [22%]; Kd, 38 [25%]). INTERPRETATION:KdD significantly prolonged progression-free survival versus Kd in patients with relapsed or refractory multiple myeloma and was associated with a favourable benefit-risk profile. FUNDING:Amgen.

摘要

背景: 来那度胺和硼替佐米一线暴露已经增加了对复发或难治性多发性骨髓瘤患者的新型治疗的需求。在一项1期研究中,卡非佐米联合达雷妥尤单抗对复发性或难治性多发性骨髓瘤显示出显著的疗效和可耐受的安全性.在这项研究中,我们旨在比较卡非佐米、地塞米松和达雷妥尤单抗与卡非佐米和地塞米松在复发性或难治性多发性骨髓瘤患者中的疗效和安全性。 方法: 在这项随机、多中心、开放标签、3期研究中,从北美、欧洲、澳大利亚和亚洲的466个研究中心招募的102例复发性或难治性多发性骨髓瘤患者2:1被随机分配至carfilzomib、地塞米松和达雷妥尤单抗 (KdD) 或carfilzomib和地塞米松 (Kd)。所有患者每周接受两次56 mg/m2的carfilzomib (20 mg/m2; 周期1期间的第1天和第2天)。在第1周期的第1天和第2天静脉内施用Daratumumab (8 mg/kg),并且对于前两个周期的剩余剂量每周以16 mg/kg施用,然后每2周施用4个周期 (周期3-6),并且此后每4周施用一次。患者每周接受40 mg地塞米松 (≥ 75岁患者从第二周开始服用20 mg)。主要终点是通过意向治疗评估的无进展生存期。在安全性人群中评估不良事件。本试验 (NCT03158688) 在ClinicalTrials.gov注册,有效但不招募。 结果: 在2017年6月13日至20 18年6月25日期间,纳入了466例患者,其中569例被评估为合格。中位随访约17个月后,KdD组未达到中位无进展生存期,Kd组为15 · 8个月 (风险比0 · 63; 95% CI 0 · 46-0 · 85; p = 0 · 0027).KdD组的中位治疗持续时间比Kd组长 (70 · 1 vs 40 · 3周)。KdD组253例 (82%) 患者和Kd组113例 (74%) 患者报告了3级或更高级别的不良事件。两组中导致治疗中止的不良事件的频率相似 (KdD,69 [22%]; Kd,38 [25%])。 解读: 与Kd相比,KdD显著延长了复发或难治性多发性骨髓瘤患者的无进展生存期,并与有利的获益-风险特征相关. 资金: 安进。

关键词:
阅读人数:6人
下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:0.81
发表时间:2020-01-01
来源期刊:Congenital anomalies
DOI:10.1111/cga.12331
作者列表:["Shahid M","Firasat S","Satti HS","Satti TM","Ghafoor T","Sharif I","Afshan K"]

METHODS::Fanconi anemia (FA) is a recessive disorder that predispose to bone marrow failure and multiple congenital anomalies in affected individuals worldwide. To date, 22 FA genes are known to harbor sequence variations in disease phenotype. Among these, mutations in the FANCA gene are associated with 60% to 70% of FA cases. The aim of the present study was to screen FA cases belonging to consanguineous Pakistani families for selected exons of FANCA gene which are known mutational hotspots for Asian populations. Blood samples were collected from 20 FA cases and 20 controls. RNA was extracted and cDNA was synthesized from blood samples of cases. DNA was extracted from blood samples of cases and ethnically matched healthy controls. Sanger's sequencing of the nine selected exons of FANCA gene in FA cases revealed 19 genetic alterations of which 15 were single nucleotide variants, three were insertions and one was microdeletion. Of the total 19 sequence changes, 13 were novel and six were previously reported. All identified variants were evaluated by computational programs including SIFT, PolyPhen-2 and Mutation taster. Seven out of 20 analyzed patients were carrying homozygous novel sequence variations, predicted to be associated with FA. These disease associated novel variants were not detected in ethnically matched controls and depict genetic heterogeneity of disease.

翻译标题与摘要 下载文献
影响因子:2.36
发表时间:2020-01-01
来源期刊:Platelets
DOI:10.1080/09537104.2019.1581922
作者列表:["Szanto T","Nummi V","Jouppila A","Brinkman HJM","Lassila R"]

METHODS::In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to in vitro thrombin generation (TG) and platelet procoagulant activity in VWD3. TG was assessed by calibrated automated thrombogram (CAT) in platelet-poor (PPP) and -rich plasma (PRP) from 9 patients before and in 6 patients also 30 min after receiving their regular VWF therapy. Responsiveness of PPP to FVIII and protein S was also investigated. TG data were compared with routine laboratory variables, rotational thromboelastometry (ROTEM) and platelet expression of P-selectin and phosphatidylserine in flow cytometry. Compared with healthy controls, TG was markedly decreased in VWD3 PPP (peak thrombin was 16% of normal median), but not in PRP (77% of normal median) (p = 0.002). Six out of nine patients (67%) were high responders in their platelet P-selectin, and 5/9 (56%) in phosphatidylserine expression. Replacement therapy improved TG in PPP, while in PRP TG only modestly increased or was unaffected. In PPP, FVIII levels associated with TG and in vitro FVIII-supplemented TG inclined up to threefold. Conversely, a FVIII inhibitory antibody reduced plasma TG in all, but especially in patients with remnant FVIII levels. Inhibition of protein S improved plasma TG, particularly at low FVIII levels. ROTEM failed to detect VWD3.In VWD3, TG is reduced in PPP and regulated by FVIII and protein S, but TG is close to normal in PRP. VWD3 platelets seem to compensate for the FVIII-associated reduction in TG by their exposure of P-selectin and phosphatidylserine.

影响因子:1.41
发表时间:2020-03-01
DOI:10.1177/1078155219843987
作者列表:["Al-Momani D","Al-Qasem W","Kasht R","Sultan I"]

METHODS:BACKGROUND:The optimal timing of initiating granulocyte-colony stimulating factor following chemotherapy in pediatric patients has not been clearly defined. This study aimed to compare the administration of granulocyte-colony stimulating factor on day 1 versus day 3 postchemotherapy in pediatric patients with Ewing sarcoma. METHOD:A retrospective study of pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor following chemotherapy between January 2016 and September 2018 at a comprehensive cancer center. The institution's chemotherapy protocol for Ewing sarcoma was modified in April 2017 to include granulocyte-colony stimulating factor initiation on day 3 instead of day 1 post-chemotherapy. Febrile neutropenia requiring hospitalization, duration of hospital stay, and chemotherapy delay were compared for patients before and after the protocol change. RESULTS:Over the study period, 250 cycles were evaluated with day 1 granulocyte-colony stimulating factor and 221 cycles with day 3 granulocyte-colony stimulating factor. There were no differences between the day 1 and day 3 groups in the number of cycles associated with Febrile neutropenia requiring hospitalization (34 vs. 19, p = 0.086), and the length of Febrile neutropenia-related hospitalization (mean 4 ± 2.1 vs. 4.6 ± 1.8, p = 0.123). However, delay in chemotherapy due to neutropenia was reported in significantly more cycles in the day 1 group, compared to the day 3 group (37 vs. 16, p = 0.01). CONCLUSIONS:Febrile neutropenia resulting in hospital admission and the length of hospital stay was not different between pediatric patients with Ewing sarcoma who received granulocyte-colony stimulating factor on day 1 or day 3 post-chemotherapy. Chemotherapy delay due to neutropenia was higher in patients who received granulocyte-colony stimulating factor on day 1. Larger studies are required to fully determine the impact of delayed initiation of granulocyte-colony stimulating factor.

翻译标题与摘要 下载文献
血液方向

主要包括小儿贫血、血友病、急性白血病及特发性血小板减少性紫癫等疾病。

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: