来那度胺联合小剂量地塞米松治疗复发难治性多发性骨髓瘤的临床观察

目的观察来那度胺联合小剂量地塞米松(Rd)治疗复发难治性多发性骨髓瘤的疗效及安全性。方法收集13例复发难治性多发性骨髓瘤患者,均给予Rd方案治疗,具体为:来那度胺25 mg/d,d1~21,地塞米松20 mg/周,28 d为1个疗程,观察疗效及不良反应。结果 2~3个疗程后,1例达到完全缓解(CR),2例达到非常好的部分缓解(VGPR),3例达到部分缓解(PR),3例疾病稳定(SD),2例疾病进展(PD),2例死亡。总有效率(ORR=CR+VGPR+PR)为46.2%。不良反应主要为乏力及骨髓抑制。结论来那度胺联合小剂量地塞米松治疗复发难治性多发性骨髓瘤近期疗效好,安全性高,可作为推荐治疗方案。     

来那度胺联合环磷酰胺、低剂量地塞米松治疗多发性骨髓瘤临床观察

目的分析来那度胺联合环磷酰胺、低剂量地塞米松治疗多发性骨髓瘤的临床效果。方法50例多发性骨髓瘤患者,采用随机分配方式分为对照组与治疗组,各25例。对照组患者采用左旋苯丙氨酸氮芥(商品名:马法兰)联合泼尼松、沙利度胺(MPT方案)治疗,治疗组患者采用来那度胺联合环磷酰胺及低剂量地塞米松(RCD方案)治疗。对比两组患者治疗效果、不良反应发生率及血β2-微球蛋白水平及尿β2-微球蛋白水平。结果对照组患者治疗显效9例,有效7例,无效9例,总有效率为64%;治疗组患者显效16例,有效6例,无效3例,总有效率为88%;治疗组患者总有效率高于对照组,差异有统计学意义(χ^2=3.9474,P<0.05)。对照组患者发生嗜睡3例,便秘3例,神经组织病变2例,不良反应发生率为32%;治疗组患者发生嗜睡1例,便秘1例,神经组织病变0例,不良反应发生率为8%;治疗组患者不良反应发生率低于对照组,差异有统计学意义(χ^2=4.5000,P<0.05)。对照组患者血β2-微球蛋白水平为(2.27±0.58)mg/L,尿β2-微球蛋白水平为(1.13±0.39)mg/L;治疗组患者血β2-微球蛋白水平为(1.71±0.42)mg/L,尿β2-微球蛋白水平为(0.81±0.29)mg/L;治疗组患者血β2-微球蛋白水平及尿β2-微球蛋白水平均低于对照组,差异具有统计学含义(t=3.9101、3.2922,P=0.0003、0.002<0.05)。结论针对多发性骨髓瘤患者采用来那度胺联合环磷酰胺、低剂量地塞米松药物治疗,能够有效缓解患者疾病发展,控制患者疾病进程,对于改善患者生活质量、提升患者生存周期具有重要意义。     

伊沙佐米联合来那度胺及地塞米松治疗复发难治性多发性骨髓瘤的疗效与安全性

目的 探讨伊沙佐米联合来那度胺及地塞米松治疗复发难治性多发性骨髓瘤的疗效与安全性。方法 将102例复发难治性多发性骨髓瘤患者随机分为对照组(51例,采用来那度胺联合地塞米松治疗)和观察组(51例,采用伊沙佐米联合来那度胺及地塞米松治疗),均以28 d为一周期,连续治疗3个周期。比较两组患者的临床疗效、化疗前后生化指标、免疫功能及不良反应。结果 治疗后观察组总缓解率(94.12%)明显高于对照组(78.43%)(P<0.05);两组患者血沉、血清M蛋白及β₂微球蛋白水平均较化疗前下降,观察组低于对照组(均P<0.05)。治疗后两组患者CD₄⁺比例及CD₄⁺/CD₈⁺均较化疗前升高,观察组高于对照组(均P<0.05),两组患者CD₈⁺比例均较化疗前降低,观察组低于对照组(均P<0.05)。化疗期间血液学不良反应发生率较高,但两组血液学及非血液学不良反应发生率比较,差异均无...     

观察来那度胺联合地塞米松治疗多发性骨髓瘤的临床疗效

目的 观察来那度胺联合地塞米松治疗多发性骨髓瘤的临床疗效。方法 52例多发性骨髓瘤患者,依据随机数字表法分为对照组及观察组,各26例。对照组给予PD方案(硼替佐米联合地塞米松)治疗,观察组给予来那度胺联合地塞米松治疗。比较两组临床疗效,实验室检查指标(β₂微球蛋白、M蛋白、血沉)水平,不良反应发生情况。结果 观察组的治疗总有效率88.46%高于对照组的65.38%,差异具有统计学意义(P<0.05)。治疗前,两组β₂微球蛋白、M蛋白、血沉水平比较,差异无统计学意义(P>0.05);治疗后,两组β₂微球蛋白、M蛋白、血沉水平均较治疗前降低,且观察组的β₂微球蛋白(1.15±0.11)mg/L、M蛋白(14.56±1.12)g/L、血沉(21.78±4.32)mm/h低于对照组的(1.89±0.43)mg/L、(17.55±2.09)g/L、(29.10±4.30)mm/h,差异具有统计学意义(P<0.05)。观察组的不良反应发生率15.38%低于对照组的46.15%,差异具有统计学意...     

应用来那度胺联合小剂量地塞米松治疗复发难治性多发性骨髓瘤的有效价值分析

目的:探讨多发性骨髓瘤(MM)患者选择来那度胺与地塞米松联合治疗的临床应用效果.方法:将我院88例复发难治性MM患者纳入研究.用计算机软件分为对照组与观察组(n=44),对照组患者选择来那度胺治疗,观察组患者在此基础上增加地塞米松治疗,治疗半年后观察两组的临床情况.结果:治疗后的观察组总有效率与治疗后的对照组存在差异(77.27％>56.82％),P<0.05.在不良反应发生率方面,观察组患者(84.09％)与对照组患者(86.36％)比较,统计学结果为χ2=0.090,P>0.05.结论:复发难治性MM患者在选择治疗方法上,可以将来那度胺(常规剂量)+地塞米松(小剂量)考虑在内.     

来那度胺联合小剂量地塞米松(Rd)治疗复发难治性多发性骨髓瘤的疗效及安全性

目的研究来那度胺联合小剂量地塞米松(Rd)治疗复发难治性多发性骨髓瘤的疗效及安全性。方法随机选取我院收治的复发难治性多发性骨髓瘤患者,共20例,收治时间在2013年2月至2016年1月期间,以此作为本次实验的主要对象,并予以所有患者来那度胺联合小剂量地塞米松(Rd)治疗,研究其治疗后的临床效果和不良反应发生情况。结果在经过3个疗程的治疗之后,20例患者中,有3例患者发生死亡情况,在其他17例患者中,主要出现的不良反应是骨髓抑制与乏力。结论对复发难治性多发性骨髓瘤患者实施来那度胺联合小剂量地塞米松(Rd)治疗,在短期内的临床效果较好,用药相对安全且有效,值得在临床中推广应用。     

三氧化二砷联合来那度胺和地塞米松治疗复发难治多发性骨髓瘤的临床分析

目的研究三氧化二砷联合来那度胺和地塞米松治疗复发难治多发性骨髓瘤的疗效及不良反应。方法 40例复发难治多发性骨髓瘤患者,随机分为对照组和实验组,每组20例。对照组给予来那度胺和地塞米松治疗,实验组在对照组基础上给予三氧化二砷治疗,比较两组疗效及不良反应。结果实验组总有效率为65%,明显高于对照组的35%,差异有统计学意义(P<0.05)。实验组血象改变、发热、便秘、恶心呕吐、心动过缓等不良反应与对照组比较差异无统计学意义(P>0.05)。结论来那度胺联合地塞米松和三氧化二砷治疗复发难治多发性骨髓瘤疗效明显,值得临床推广应用。     

来那度胺联合化疗治疗多发性骨髓瘤9例护理

目的探讨来那度胺联合化疗治疗多发性骨髓瘤的护理方法,以减少并发症的发生。方法对我科近两年来收治的9例复发难治性多发性骨髓瘤患者化疗期间可能出现的心理和化疗副作用进行有针对性的系统护理。结果患者并发症发生程度较轻,同时掌握了相关并发症的预防和自我护理方法。结论有效的观察、专业的护理、全面的健康教育,可明显减少化疗患者的并发症,对提高患者的生活质量、促进疾病康复有重要意义。     

来那度胺在多发性骨髓瘤治疗中的应用

多发性骨髓瘤目前仍是无法治愈的恶性血液系统疾病,复发、耐药、治疗相关毒性仍是阻碍患者生存的重要因素。来那度胺是新一代免疫调节剂,具有抗血管生成、改善免疫功能和肿瘤杀伤、改变骨髓微环境等独特的多重的作用机制。来那度胺在复发难治性多发性骨髓瘤的治疗中显著延长了无进展生存期(PFS)和总生存率。在新诊断的多发性骨髓瘤初始治疗中也获得了较高的缓解率。它在巩固维持治疗中更是显著延长了PFS和生存期,为长期"控制"多发性骨髓瘤提供了新的治疗策略。     

Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes

Recently, outcomes for patients with multiple myeloma have improved dramatically due to improved and innovative therapies. However, most patients will either relapse or become refractory to current therapy. Thus, a significant unmet need remains for novel agents to treat this patient population. Panobinostat, a potent pan-deacetylase inhibitor with a unique mechanism of action targeting both epigenetic regulation of gene expression and protein metabolism, has preclinical synergy with a number of agents, including the proteasome inhibitor bortezomib. In a phase 3 trial of panobinostat with bortezomib and dexamethasone, addition of panobinostat significantly prolonged the median progression-free survival of patients with relapsed or relapsed and refractory multiple myeloma. This review focuses on clinical development of panobinostat, with particular emphasis on pharmacokinetics and adverse event management.     

沙利度胺联合地塞米松治疗难治性复发性多发性骨髓瘤的临床疗效

目的评价沙利度胺单独或联合地塞米松治疗难治性复发性多发性骨髓瘤(MM)的临床疗效。方法42例难治性复发性MM患者,单用组20例:沙利度胺起始剂量100 mg.d-1,每周增加100 mg,直至患者最大耐受剂量或最大剂量600 mg.d-1。联合组22例:在沙利度胺治疗剂量至200 mg.d-1时,给予地塞米松40 mg.d-1(d 1~4、9~121、7~20),1 mo为1个疗程。持续治疗3 mo。结果单用组总有效率35.0%,明显低于联合组68.2%(P<0.05)。结论沙利度胺能有效治疗难治性复发性MM,在联合地塞米松时可提高有效率。     

How to treat patients with relapsed/refractory multiple myeloma: evidence-based information and opinions

Introduction: Relapsed/refractory multiple myeloma (rrMM) remains a difficult condition to treat despite the availability of new drugs. This review aims to provide evidence to guide physicians in the choice of salvage therapy in certain subgroups of patients.

Areas covered: The review attempts to present evidence-based information and suggest possible approaches based on data on previous therapies, previous remission duration and toxicity of previous treatments, patient's co-morbidities and disease characteristics at relapse. Unfortunately, little evidence is available; there are no large and/or randomized trials, direct comparisons of drugs or combinations for rrMM patients to draw any definite conclusion.

Expert opinion: Almost all the studies presented here suggest that depth of response is a key factor also for patients with rrMM. Identifying the best approach between combinations and sequential therapies remains controversial. Several studies favor the former approach in early relapse as it leads to a higher complete response rate, regardless of previous therapies. However, in both strategies, achieving maximal response should always remain a main goal. Consolidation/maintenance therapy is beneficial both in combination and sequential therapies also in rrMM. Second generation new drugs, such as pomalidomide, carfilzomib, bendamustine and HDAC inhibitors, will probably expand the rescue possibilities also in this setting.     

The clinical safety of lenalidomide in multiple myeloma and myelodysplastic syndromes

Thionamides, selective inhibitors of thyroid peroxidase-mediated iodination by tyrosine residues in thyroglobulin, have been effectively used in the treatment of hyperthyroidism. The choices for initial treatment of patients with Graves’ disease differ in various countries, and many physicians around the world prefer to administer thionamide drugs as the first choice of treatment for patients with hyperthyroidism. Although some thyroidologists more often consider radioiodine to be the treatment of choice because of its safety and ease of administration, thionamides remain the mainstay of treatment in thyrotoxic children and adolescents and in hyperthyroid women during pregnancy, postpartum period and lactation. A recent study with continuous thionamide treatment for patients with Graves’ disease shows its efficacy, safety and cost-benefit properties. Further studies of the effectiveness of continuous thionamide therapy in patients with thyrotoxicosis need to be designed and implemented to determine indications for such therapy in children, adolescents and adults with diffuse toxic goiter, in particular, in those who have had recurrence of hyperthyroidism after discontinuation of one complete course of treatment.     

An update on the use of lenalidomide for the treatment of multiple myeloma

Introduction: Lenalidomide, an immunomodulatory agent with unique mechanism of action, represents the cornerstone in the treatment of patients with multiple myeloma (MM) providing rapid and sustained control of the disease with a manageable safety profile.

Areas covered: This review article, synthesizing all available data coming from trials and evaluating the efficacy and safety of lenalidomide in patients with MM, tries to provide to the clinicians with an easy-to-grasp synopsis of recent and clinically meaningful advances on the field.

Expert opinion: Lenalidomide combined with dexamethasone is a safe and effective option for newly diagnosed MM patients ineligible for autologous stem cell transplantation (ASCT). Long-term administration of the agent as continuous treatment for ineligible for ASCT patients or maintenance therapy after ASCT has documented unprecedented progression-free survival improvements, whereas lenalidomide in combination with dexamethasone has shown deep and durable remissions for patients with relapsed and/or refractory disease.     

Lenalidomide in multiple myeloma: current role and future directions

Importance of the field: Lenalidomide and other new agents are improving survival of multiple myeloma patients. This review describes current data on lenalidomide in myeloma and how the unique properties of lenalidomide may lend its use in new settings, such as maintenance and preventive therapy.

Areas covered in this review: This review covers the activity of lenalidomide in multiple myeloma, efficacy in both newly diagnosed and relapsed/refractory patients, how to manage effectively common adverse events observed with lenalidomide, and its potential use in new settings based on clinical trials published up to 2009.

What the reader will gain: This review describes the mechanism of action of lenalidomide in myeloma which provides the basis for its clinical use in newly diagnosed, relapsed/refractory, and high-risk smoldering myeloma in combination with other agents. Strategies to reduce or effectively manage myelosuppression and thromboembolic events, the main adverse events associated with lenalidomide plus dexamethasone therapy, are also described.

Take home message: Lenalidomide is an oral immunomodulatory drug that is highly effective in treating multiple myeloma, has a favorable safety profile and is now being evaluated as maintenance therapy, preventive therapy and in combination with other new agents.     

VTD方案治疗复发难治性多发性骨髓瘤36例

目的观察硼替佐米联合沙利度胺、地塞米松（VTD）方案治疗多发性骨髓瘤的疗效和不良反应。方法采用VTD方案治疗复发难治性多发性骨髓瘤患者36例。结果36例患者平均完成3．8个疗程,总有效率为80．6％。主要不良反应为血小板减少、乏力、周围神经病变等。结论VTD方案治疗复发难治性多发性骨髓瘤的疗效好,且不良反应少、易耐受。     

Current therapeutic uses of lenalidomide in multiple myeloma

Thalidomide has demonstrated a broad spectrum of pharmacological and immunological effects, with potential therapeutic applications that span a wide spectrum of diseases: cancer and related conditions; infectious diseases; autoimmune diseases; dermatological diseases; and other disorders such as sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory derivative lenalidomide has more potent antitumour and anti-inflammatory effects. The molecular mechanisms of antitumour activity of lenalidomide have been extensively studied in multiple myeloma (MM). It directly induces growth arrest and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to bone marrow extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the bone marrow milieu; and augments host antitumour immunity. Importantly, lenalidomide induces significant clinical responses even in patients with relapsed/refractory MM. Therefore, lenalidomide represents a new class of antitumour agents that is useful in the treatment of MM. Lenalidomide has received fast track designation from the FDA for the treatment of MM and myelodysplastic syndromes.     

硼替佐米联合沙利度胺治疗复发、难治性多发性骨髓瘤的疗效与安全性观察

目的:观察硼替佐米联合沙利度胺治疗复发、难治性多发性骨髓瘤的疗效与安全性.方法:收集我院2007年3月至2010年12月采用硼替佐米联合沙利度胺方案治疗复发、难治性多发性骨髓瘤患者的临床资料进行回顾性分析.治疗方法为硼替佐米1.3 mg/m2,于第1、4、8、11天静脉注射;沙利度胺100 mg/d,口服;21 d为1个疗程.依据欧洲血液及骨髓移植组标准判定疗效,按CTCAE Version 3.0标准评价不良反应.结果:共有66例复发、难治性多发性骨髓瘤患者接受硼替佐米联合沙利度胺治疗,除外因个人原因未完成治疗的7例患者,共有59例患者的资料纳入分析.59例中男37例,女22例,中位年龄51(30 ～64)岁.中位疗程数为6(2～8),中位观察期5(2～10)个月,59例患者中有6例获得完全缓解,12例获得部分缓解,20例获得轻微缓解,总有效率为64.4％.最常见不良反应为胃肠道症状(42例,其中出现不同程度恶心或呕吐36例次,腹泻29例次),其他不良反应为乏力(37例)、血小板减少(23例)、肢端麻木(18例)、发热(15例)、憋气、心慌(5例)、体位性低血压(4例),有1例患者出现视觉障碍.经减少用药剂量或停药及对症治疗后均获缓解.结论:硼替佐米联合沙利度胺是治疗复发、难治性多发性骨髓瘤的有效方法,同时具有较好的安全性.