Melphalan: old and new uses of a still master drug for multiple myeloma

The treatment of multiple myeloma has seen significant changes from the initial use of melphalan to the introduction of stem cell transplantation and, most recently, to the era of novel targeted agents. Melphalan still remains as a reference drug for combination regimens, including emerging newer therapeutic options, either used at a standard dose for initial or salvage treatments in patients who are not eligible for more intensive therapies, or in conjunction with new molecules within high-dose chemotherapy programs. In this review, the authors analyze old and novel regimens, including melphalan for the treatment of newly diagnosed or relapsed/resistant patients with multiple myeloma in the clinical settings of standard chemotherapy, as well as autologous or allogeneic stem cell transplantation.     

地塞米松联合硼替佐米对老年多发性骨髓瘤的治疗效果

目的 分析地塞米松联合硼替佐米对老年多发性骨髓瘤的治疗效果。方法 选择2014年1月—2016年12月在宿州市市立医院血液科进行诊治的41例老年多发性骨髓瘤患者,随机分为两组,观察组21例,对照组20例。两组均给予沙利度胺和环磷酰胺进行治疗,分别口服沙利度胺100 mg,1次/d,并分别于第1、8、15天静滴环磷酰胺300 mg/m²。同时,对照组于第1~4天静脉滴注地塞米松20 mg。观察组在对照组基础上皮下注射硼替佐米1.3 mg/m²,1次/周,1个疗程为4周,2个疗程后进行综合评价。比较两组的临床治疗效果,检测两组治疗前后的β2微球蛋白、骨髓瘤细胞以及免疫球蛋白水平及不良反应。结果 观察组的有效率为85.71%,明显高于对照组的60.00%,差异有统计学意义（P<0.05）。两组治疗后的β2微球蛋白、骨髓瘤细胞以及免疫球蛋白水平均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组明显低于对照组,差异有统计学意义（P<0.05）。两组间各不良反应的发生率无统计学差异,且各不良反应通过停药或给予相应对症处理后均可得到缓解。结论 地塞米松联合硼替佐米治疗老年多发性骨髓瘤的临床效果明显,可作为初治、难治或复发老年多发性骨髓瘤患者的一线治疗方案。     

沙利度胺联合MP方案治疗老年多发性骨髓瘤临床观察

目的 观察沙利度胺联合MP方案(马法兰、强的松)与单用MP方案比较治疗老年多发性骨髓瘤(MM)的临床疗效及安全性.方法 治疗组(24例)口服沙利度胺,同时联合MP方案化疗,每月1个疗程.对照组(22例)单用MP方案化疗,马法兰、泼尼松的剂量和用法同治疗组.在4个疗程后,判断2组疗效及不良反应.结果 治疗组总有效率79....     

多发性骨髓瘤药物治疗新进展

多发性骨髓瘤(MM)是一种常见的血液系统恶性肿瘤,主要集中在老年人,40 a以下者少见。尽管传统化学治疗(化疗)MP、M2、VAD仍是初治Ⅰ、Ⅱ期MM的首选方法,但有效率不高且不能治愈。新的化疗组合和老药沙利度胺的新用已使MM缓解率和无病生存期明显提高,来那度胺、硼替佐米、三氧化二砷、二膦酸盐类等用于复发、难治性MM取得了更高的缓解率,同时也相信尚在实验室研究中的新药会给MM的治疗带来新的希望。     

Lenalidomide in combination or alone as maintenance therapy following autologous stem cell transplant in patients with multiple myeloma: a review of options for and against

Introduction: Lenalidomide has multifaceted antimyeloma properties, including direct tumoricidal and immunomodulatory effects. Several randomized controlled trials have demonstrated improved patient outcomes with lenalidomide maintenance after autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM). Currently, single-agent lenalidomide is the only approved post-ASCT maintenance therapy in the United States and European Union for patients with NDMM.

Areas covered: This review article summarizes the efficacy and safety data of lenalidomide maintenance, as monotherapy and in combination with other agents, following ASCT in patients with NDMM. In addition, emerging therapies with newer agents in this setting are discussed.

Expert opinion: Following ASCT, maintenance therapy with lenalidomide until progressive disease is an effective and well-tolerated regimen and represents the standard of care for patients with NDMM. Studies evaluating maintenance with lenalidomide in combination with next-generation proteasome inhibitors, monoclonal antibodies, and histone deacetylase inhibitors may further improve patient outcomes.     

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.     

沙利度胺联合地塞米松治疗老年多发性骨髓瘤的疗效分析及不良反应

目的观察沙利度胺联合地塞米松治疗老年多发性骨髓瘤的疗效和安全性。方法初治老年多发性骨髓瘤患者50例,均给予沙利度胺联合地塞米松治疗,沙利度胺起始剂量50 mg/次,1次/d,口服,根据患者耐受情况逐步增加剂量50mg,至最大量200 mg/次,1次/日,口服;地塞米松20 mg/次,1次/日,第1～4天,第9～12天,第17～20天,静脉滴注,每28 d为1个疗程。治疗4个疗程后评定疗效。结果完全缓解15例,非常好的部分缓解12例,部分缓解13例,病情无变化5例,疾病进展5例,总有效率为80%。治疗过程中出现嗜睡l7例,便秘16例,疲乏16例,血糖升高10例,外周神经炎8例,皮疹3例,对症处理后均可耐受。结论沙利度胺联合地塞米松是治疗老年多发性骨髓瘤的有效方法。     

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。     

Commentary on pharmacotherapy of regional melanoma therapy

Importance to the field: Regional therapy continues to be the workhorse for the treatment of regional metastases and unresectable recurrences of melanoma limited to a limb. These approaches also offer an excellent opportunity for the study of disease biology and new drug delivery, pharmacokinetics and pharamacotherapeutics.

Areas covered in this editorial: Utility of regional therapy as an area of study, benefits of both isolated limb infusion (ILI) and hyperthermic isolated limb perfusion (HILP) are discussed. The limitations of both approaches to regional therapy are also referenced.

What the reader will gain: This editorial serves as a companion to the peer-reviewed paper which comprehensively reviews the subject of regional therapy by Tyler et al. It offers a brief commentary on the utility of regional therapies (ILI and HILP) for extremity in-transit melanoma and their role in investigating new therapeutic modalities.

Take home message: Regional therapy is an excellent therapeutic modality for disease limited to a limb and furthermore serves as an excellent model for scientific investigation, both clinical and translational.     

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.     

Novel immunomodulatory compounds in multiple myeloma

Introduction: The treatment options for patients with multiple myeloma (MM) remain limited. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have changed the landscape in the treatment of patients with MM while newer IMiDs such as pomalidomide are showing promise in early clinical trials.

Areas covered: This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MM. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search and abstracts from oncology scientific meetings (ASCO and ASH) of articles related to IMiDs and MM was conducted.

Expert opinion: IMiDs have shown clinical activity as single agents and in combination. Thalidomide was the first in class drug. Lenalidomide has a better toxicity profile than thalidomide. Pomalidomide may overcome resistance to lenalidomide indicating differences in their mechanisms of action and resistance. Molecular biomarkers may allow us to identify patients who will respond to IMiDs.     

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.     

Current treatments for renal failure due to multiple myeloma

Introduction: Renal impairment (RI) is a common complication of symptomatic myeloma; 20 – 40% of newly diagnosed patients present with moderate or severe RI and 10% of them may require dialysis. Immediate initiation of specific antimyeloma therapy is crucial in order to improve RI.

Areas covered: There has been a significant improvement in the outcome of patients with RI over the past 15 years. The authors review current data on the role of antimyeloma therapy on the improvement or resolution of RI and the importance of novel regimens, especially those based on bortezomib. IMiDs-based regimens, conventional chemotherapy and high-dose therapy is also reviewed. The role of extrarenal free light chain removal, by means of plasma exchange or extended hemodialysis with the use of high cutoff dialysis membranes, is also discussed.

Expert opinion: Bortezomib/dexamethasone-based regimens are the preferred regimens for most patients with multiple myeloma (MM) who present with RI, especially for newly diagnosed patients; however, other novel agents (thalidomide, lenalidomide) in combination with dexamethasone may also improve RI in several patients. Further investigation is needed for the clarification of the role of plasma exchange or extended high cutoff dialysis. Carfilzomib, which was recently approved, may also be a treatment choice for selected patients with relapsed MM and RI.     

小剂量硼替佐米联合化疗治疗4例多发性骨髓瘤的疗效

目的观察小剂量硼替佐米联合化疗治疗复发难治或初发多发性骨髓瘤（MM）的疗效和不良反应。方法4例MM患者接受硼替佐米＋环磷酰胺＋地塞米松＋沙利度胺治疗,每3周为一疗程。所有患者接受2～4疗程的治疗。采用EBMT疗效标准评价疗效,按国立癌症研究所的常规毒性判定标准评价不良反应。结果4例MM患者中1例接近完全缓解,3例部分缓解。不良反应有白细胞减少、血小板减少、肺部感染等。结论小剂量硼替佐米联合化疗可作为复发难治或初发MM的治疗选择。     

波替单抗为主的化疗方案治疗多发性骨髓瘤的安全性观察

目的:评价以波替单抗为主的2种化疗方案治疗多发性骨髓瘤(MM)的安全性.方法:应用不良事件标准(3.0版)对分别用PAD和VMP方案治疗的MM患者出现的不良反应进行回顾性总结分析:PAD方案:波替单抗+盐酸表柔比星+地塞米松,4个疗程,第1疗程18 d,第2～4疗程各11 d;适用于身体状况尚可、年龄较轻的MM患者.VMP方案:波替单抗+美法仑+泼尼松,4个疗程,每个疗程均11 d;适用于身体状况较差、年龄较大的MM患者:结果:2008年3月至2010年12月,共16例MM住院患者在空军总医院接受化疗.接受PAD方案者12例,男7例,女5例,中位年龄61岁;接受MVP方案者4例,男3例,女1例,中位年龄67岁.PAD与VMP方案导致的主要不良反应为血小板减少、中性粒细胞减少、周围神经病变、感染和消化道反应.(1)接受PAD方案者有9例在第2～4疗程血小板减少,其中Ⅰ～Ⅱ级7例,Ⅲ级和Ⅳ级各1例;接受VMP方案者有2例血小板减少,Ⅱ级1例,Ⅳ级1例.上述患者均持续PAD或VMP治疗未停药,Ⅲ级和Ⅳ级者输注血小板后血小板计数恢复正常.(2)接受PAD方案者有8例在第2～4疗程中性粒细胞降低,Ⅰ～Ⅱ级5例,Ⅲ级1例,Ⅳ级2例.接受VMP方案者有2例在第2～4疗程中性粒细胞降低,Ⅱ级1例,Ⅳ级1例.Ⅰ～Ⅱ级者均持续治疗未停药.接受PAD方案Ⅲ级者暂时停药给予对症治疗,中性粒细胞计数恢复正常后继续治疗.接受VMP方案Ⅳ级者未停药,皮下注射重组人粒细胞刺激因子.(3)接受PAD方案者有4例出现周围神经病变,Ⅰ～Ⅱ级3例,Ⅲ级1例.接受VMP方案者有1例出现Ⅰ级周围神经病变.1例Ⅱ级者经调整波替单抗剂量(由1.3 mg/m2减至1.0 ms/m2)后好转;1例Ⅲ级者经停药和对症治疗后恢复PAD方案;其他患者均未停药.(4)接受PAD方案者有4例在第2～4疗程出现发热和感染,1例因肺部感染发生感染性休克死亡.(5)16例患者均出现食欲减退、恶心、呕吐、腹泻或便秘,均未停药并予对症治疗.结论:PAD与VMP方案治疗MM均较安全,大多不良反应为轻度能耐受.对较严重的不良反应应停药或调整波替单抗的剂量.     

沙利度胺治疗多发性骨髓瘤的临床疗效

目的 :探讨沙利度胺治疗多发性骨髓瘤 (MM)的临床有效性。方法 :初治、难治或复发MM患者 10例 ,沙利度胺起始剂量 5 0～ 2 0 0mg·d-1,每 2wk增加 5 0～ 2 0 0mg·d-1,直到患者能够耐受或有效 ;同时联合应用化疗。根据M蛋白评定疗效为完全缓解 (CR)、很好的部分缓解 (VGPR)、部分缓解 (PR)、微小反应 (MR)和无反应 (NR)。同时对贫血、骨髓浆细胞比例和其他如口腔溃疡等进行评价。结果 :CR 3例 ,VGPR 3例 ,PR 4例。平均随访时间 5 0 5wk ,总生存率 90 %,无病生存率 30 %。无不能耐受的不良反应。结论 :沙利度胺可作为初发或难治MM的治疗。     

硼替佐米治疗复发、难治性多发性骨髓瘤

目的:观察硼替佐米治疗复发、难治性多发性骨髓瘤(MM)的疗效和不良反应。方法:6例复发、难治性MM病人,予硼替佐米3.5mg静脉注射,每周1次,共4次,在第2与第3次之间间歇1wk。每次静脉注射硼替佐米之前予地塞米松40mg加入5%葡萄糖注射液500mL中静脉滴注。采用EBMT标准观察治疗疗效,并按WHO标准判断不良反应。结果:治疗后,1例病人接近完全缓解,4例部分缓解,1例病情稳定,但在部分缓解的病人中有1例随后死于肿瘤中枢神经系统浸润。2例病人发生腹泻、血小板减少和乏力,经对症治疗后均获缓解。结论:对于经过反复治疗的复发、难治性MM,硼替佐米是一种新的治疗选择。     

沙利度胺治疗多发性骨髓瘤及其不良反应的观察

了解沙利度胺治疗多发性骨髓瘤时发生的不良反应。方法:观察32例多发性骨髓瘤应用沙利度胺期间不良反应的发生情况。结果:沙利度胺不良反应的总发生率为94％,消化系统不良反应87.5％,神经精神系统不良反应84.4％,其它不良反应有窦缓、逸搏心率、药物热、皮疹、水肿等。结论:不良反应以消化及神经系统的症状最常见,停药及减量可减少不良反应的发生,出现不良反应的原因与剂量大小及个体差异有关。