Fortschritte in der Behandlung von Patienten mit multiplem Myelom

Several therapeutic milestones have been achieved in the treatment of multiple myeloma with the alkylator melphalan being the backbone since the 1960’s. This drug is currently used at high doses followed by autologous stem cell transplantation (ASCT) to ameliorate hematologic toxicity in patients up to 70 years old. In subjects eligible for ASCT, initial cytoreduction should nowadays be performed using one of the novel compounds, thalidomide, bortezomib or lenalidomide, in combination with dexamethasone due to enhanced response both before and after ASCT when compared to standard anthracycline/dexamethasone treatment. However, it has not yet been determined which combination should best be used in a given patient. Whether consolidative or maintenance treatment with either of these drugs further improves prognosis still needs confirmatory results from currently ongoing clinical trials.     

新药时代多发性骨髓瘤的维持治疗:第57届美国血液学会年会报道

近年来,多发性骨髓瘤(MM)的新药治疗发展迅速,但患者在目前已有的治疗条件下,疾病仍然在缓解与复发中反复.越来越多的证据表明,MM患者在最终治疗后接受长期维持治疗有助于抑制残留病灶,延长缓解期,并延迟复发.对于接受自体干细胞移植(ASCT)的MM患者,来那度胺维持治疗可以提高无进展生存(PFS)率,但并不延长总生存(OS)时间.对于不适合接受ASCT的MM患者,一项大型Ⅲ期临床研究对持续来那度胺加低剂量地塞米松治疗与标准的固定疗程美法仑、 泼尼松加沙利度胺治疗进行了比较,中期分析结果显示前者的PFS及OS优于后者.其他试验也就ASCT患者沙利度胺及硼替佐米维持治疗进行了研究,这两种药物也可作为不适合ASCT患者的维持治疗.然而,关于最佳治疗方案及持续时间等问题还需要通过前瞻性临床试验得出结论,但目前一致认为,维持治疗应该作为MM的常规治疗.文章对第57届美国血液学会(ASH)年会报道的MM维持治疗的相关研究进行回顾分析,以明确维持治疗在MM治疗中的作用.     

Management of newly diagnosed myeloma

The treatment of multiple myeloma has changed dramatically in the last decade with the introduction of thalidomide, bortezomib, and lenalidomide. Patients eligible for autologous stem cell transplantation (ASCT) are treated with non-alkylating agent-containing regimens as initial therapy; typically thalidomide-dexamethasone or lenalidomide-dexamethasone. For patients not eligible for ASCT, the current standard of care is melphalan, prednisone, and thalidomide. Ongoing trials will soon assess if combinations including melphalan and prednisone plus bortezomib or MP plus lenalidomide may be considered an attractive option. Patients who have risk factors, such as deletion 13 or translocation t(4;14) or t(14;16), are candidates for novel, more aggressive treatments.     

新药诱导后自体造血干细胞移植对以荧光原位杂交分层的多发性骨髓瘤患者的价值

 　目的　评价新药诱导后自体造血干细胞移植（ASCT）对荧光原位杂交（FISH）标危及高危多发性骨髓瘤患者生存的影响。方法　回顾性分析74例多发性骨髓瘤患者,均接受以硼替佐米和（或）沙利度胺为主的诱导化疗,按FISH检测结果及诱导后是否接受ASCT分为标危移植组、标危化疗组、高危移植组及高危化疗组4组,通过生存分析分别评价ASCT对标危及高危患者生存的影响。结果　74例患者经新药诱导后总缓解率为91.9 %（68／74）,接近完全缓解（nCR）+ 完全缓解（CR）率为62.2 %（46／74）。FISH标危的患者与高危的患者诱导后缓解率分别为93.2 %（41／44）与86.7 %（26／30）（P＝0.592）,nCR+CR率分别为56.8 %（25／44）与70.0 %（21／30）（P＝0.251）。FISH标危的患者中,接受移植的患者与接受化疗巩固的患者无进展生存（PFS）及总生存（OS）差异均无统计学意义（P值分别为0.642和0.652）,而FISH高危的患者中,接受移植的患者比接受化疗巩固的患者PFS延长19.7个月（P＝0.028）,OS延长12.5个月（P＝0.542）。结论　在以硼替佐米和（或）沙利度胺为主的方案诱导后,ASCT对 FISH标危多发性骨髓瘤患者的PFS和OS均没有影响,但可使FISH高危患者的PFS延长。     

多发性骨髓瘤的诊治更新：第19届欧洲血液学会年会报道

多发性骨髓瘤（MM）骨病的病理生理机制不明且较复杂.在MM早期阶段,破骨细胞的骨吸收增强,骨髓瘤细胞可能依赖骨细胞而生长和存活,随着肿瘤负荷的加重,成骨细胞引起的骨形成受抑制持续存在.骨髓形态及M蛋白仍是MM诊断的基础,鉴别克隆性浆细胞流式细胞术有优势.如果患者治疗缓解后又出现明显M蛋白复发,国际骨髓瘤工作组（IMWG）专家的共识认为需要重新开始治疗,即使新的终末器官损害证据或症状尚未出现.美法仑（M）和泼尼松（P）与沙利度胺（T）或硼替佐米（Ⅴ）组成的M PT或VMP方案是新诊断老年MM患者（不适合进行自体干细胞移植）的标准治疗选择,病情缓解后给予雷那度胺和小剂量地塞米松的方案作为后续新的标准维持治疗已逐渐被接受.在老年患者治疗时,要充分意识到老年患者的虚弱较肾功能和细胞遗传学异常更影响患者的总生存（OS）,需要结合其影响制定个体化的治疗方案.     

Second primary malignancies in multiple myeloma: an overview and IMWG consensus

BackgroundTherapeutic advancements following the introduction of autologous stem cell transplantation and ‘novel’ agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians.DesignA Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review.ResultsOverall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients’ survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide.ConclusionIn general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.     

New Approaches to Smoldering Myeloma

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of one or both features of serum M-protein ≥?30 g/L and bone marrow plasma cell infiltration ≥?10 %. However, myeloma-related symptomatology is absent from this condition. The risk of progression to active MM is not uniform, and several markers are useful for identifying SMM patients at high risk of progression to active MM. These include the size of the M-protein and the infiltration in the bone marrow, the serum-free light-chain ratio, the presence of immunoparesis and percentage of plasma cell with aberrant phenotype by flow cytometry, or the presence of focal lesions in magnetic resonance imaging. Overall, the presence of these factors identifies patients who have a 50 % probability of progression at 2 years, and the forthcoming challenge will be to identify ultra-high-risk patients who have an 80 % risk of progression at 2 years. The current standard of care is not to treat until progression to symptomatic disease occurs. Several trials of melphalan, thalidomide and bisphosphonates have been conducted in the overall SMM patient population to examine the delay in time to progression (TTP) to symptomatic disease, but these have shown no significant benefit. However, a randomized trial that focused on high-risk SMM patients allocated to receive early treatment with lenalidomide plus dexamethasone versus observation did report a significant benefit with respect to TTP and overall survival. In summary, high-risk SMM patients should be targetted for early treatment, and more so efforts should be made to identify the ultra-high-risk subgroup within the high-risk SMM patient population which may be considered as early MM and thereby candidates for receiving therapy before they develop myeloma-related symptomatology.     

自体干细胞移植治疗伴有严重肾功能不全的多发性骨髓瘤

 肾衰竭是多发性骨髓瘤（MM）患者常见的临床表现。伴有肾衰竭的MM患者对传统化疗的总缓解率为35 %～50 %（完全缓解少见）,中位生存期为4个月～1年,均显著低于肾功能正常患者。有许多中心应用大剂量美法仑以及自体干细胞移植（ASCT）治疗伴有严重肾衰竭的MM患者。目前研究发现,患者肾功能严重程度以及是否接受透析对干细胞动员以及干细胞植入无明显影响。大剂量美法仑以及ASCT后,伴有肾衰竭MM患者的完全缓解率、无事件生存率以及总生存率,分别增加到30 %、20个月以及40个月左右。相当一部分患者脱离透析。但是,该领域存在的问题仍然相当多,如APBSCT导致较高的移植相关死亡率。另外,在沙利度胺、硼替佐米以及雷利度胺等新药应用于临床之后,对于ASCT治疗伴有肾衰竭MM患者的影响如何,也需要进一步探讨。     

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.     

New treatment approaches for older adults with multiple myeloma

The incidence of multiple myeloma (MM) increases with age, and with the aging of the population, the number of adults with MM is expected to double in the next 20 years. Novel agents, including the immunomodulatory agents thalidomide and lenalidomide, and the proteosome inhibitor bortezomib have dramatically changed the treatment of multiple myeloma in the past decade. The purpose of this review was to examine the recent clinical therapeutic trials in older adults with MM. A number of trials have evaluated the addition of novel agents to the traditional backbone of melphalan and prednisone. The combination of thalidomide with melphalan and prednisone has been evaluated in 7 randomized trials. The combination improves response rates and, in meta-analyses, survival, but at the expense of increased toxicity. Other combination regimens that include lenalidomide or bortezomib likewise are associated with higher response rates, but at the expense of greater toxicity. High dose dexamethasone is excessively toxic in older adults and should be avoided. The roles for high-dose therapy with autologous stem cell transplant or intermediate-dose melphalan with autologous stem cell transplant in older adults with MM in the era of modern therapy remain to be defined. In summary, there are a number of new therapeutic options for older adults with MM, allowing an individualized treatment strategy based on the patient's comorbidities and goals of care.     

Treatment of myeloma in patients not eligible for transplantation

Opinion statement Multiple myeloma (MM) remains an incurable disease for most patients, with a median survival of 4 to 5 years. High-dose chemotherapy followed by transplantation has resulted in improvement in response rates and survival compared with conventional therapy, but relapse is nearly universal and not all patients are candidates for this option of aggressive treatment. Standard therapeutic strategies for newly diagnosed patients not eligible for transplantation include pulsed high-dose dexamethasone, melphalan with prednisone, and vincristine in combination with doxorubicin and dexamethasone, as well as other combinations of alkylating agents. Emerging therapies under clinical investigation for first-line therapy include thalidomide, the thalidomide analog lenalidomide, and the proteasome inhibitor bortezomib alone and in combination with other agents, particularly dexamethasone. At an interim analysis, thalidomide combined with melphalan and prednisone was shown to induce a complete or near complete remission (CR) rate of 28% and overall (complete + partial) response rate of 77% in elderly patients generally not eligible for transplantation. These results are comparable to those obtained with high-dose therapy and may obviate transplantation in these patients. Induction therapy with bortezomib-based combinations induces complete and near complete remissions in a similar proportion of patients. These regimens include bortezomib and dexamethasone alone and in combination with doxorubicin, thalidomide, or melphalan. Use of thalidomide or bortezomib does not preclude stem cell harvest. Survival benefits need to be firmly established before these novel regimens emerge as the new standard of care for newly diagnosed disease. However, front-line treatment with combinations involving these agents is a promising strategy that may improve the standard of care for patients both eligible and ineligible for stem cell transplantation.     

Multiple myeloma in the elderly: when to treat, when to go to transplant

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.     

多发性骨髓瘤固定周期治疗和连续治疗的研究进展

多发性骨髓瘤(MM)占血液系统恶性肿瘤的13％,常发生于老年人群.新药物和治疗方法的引入使患者的生存期显著延长,但是患者在不同治疗阶段仍会复发.有研究证实,在行自体造血干细胞移植的患者中,应用来那度胺、硼替佐米或硼替佐米联合方案巩固治疗,可提高标危或高危患者的无疾病进展生存期;在不适合移植的患者中,应用来那度胺联合地塞米松方案连续治疗的患者,比应用美法仑联合泼尼松、沙利度胺方案固定周期治疗的患者生存期长,优化治疗方案是目前合适的选择.文章对移植后及不适合移植患者的固定周期治疗和连续治疗的效果进行介绍.     

Induction Treatment With Cyclophosphamide,Thalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: A Phase II Study

Background:Thalidomide has alternative mechanisms of action; it can be combined with dexamethasone or alkylating agents for the treatment of multiple myeloma (MM); however, the optimal doses and appropriate intervals of thalidomide continue to be debated.Patients and Methods:We assessed the clinical efficacy and toxicity of thalidomide in patients with newly diagnosed MM; 68 patients were treated with pulsed cyclophosphamide, thalidomide, and dexamethasone (CTD) chemotherapy for induction treatment.Results:After a median of 28 months' follow-up, the overall response rate was 79.4%, with a 42.6% complete response (CR) or very good partial response (VGPR). Patients with cytogenetically high-risk disease had poor CR/VGPR rates (27.3%) at a median of 11.5 months of time to progression (TTP) compared with patients with standard-risk disease who achieved CR/VGPR rates (50%) at a median of 20.3 months of TTP. The major adverse events included peripheral sensory neuropathy (14.3%), infection (10.2%), and thromboembolic complications (5.9%). Thirty-two patients who achieved more than a PR proceeded to peripheral blood stem cell collection with a median number of 5.0 × 10⁶ CD34⁺ cells/kg collected.Conclusion:CTD resulted in a favorable response with tolerable toxicity in patients with MM and did not affect the yield of the stem cell collection.     

Phase II trial of syncopated thalidomide, lenalidomide, and weekly dexamethasone in patients with newly diagnosed multiple myeloma

IntroductionOver the past decade, the novel agents thalidomide, lenalidomide, and bortezomib have emerged as effective treatment in patients with multiple myeloma (MM). Initially used in the relapse setting, these agents have been incorporated into frontline treatment algorithms. They have been combined in doublets with corticosteroids, in triplets with alkylators, or with each other. Because thalidomide and lenalidomide have different clinical activity and toxicity profiles, we designed a trial to evaluate a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone in patients with newly diagnosed MM to determine response and toxicity.Patients and MethodsTwenty-two patients with newly diagnosed MM were treated with syncopated thalidomide (200 mg on days 1-7 and 15-21), lenalidomide (25 mg on days 8-14 and 22-28 for the first cycle and 50 mg on the same schedule for subsequent cycles) with weekly dexamethasone (40 mg). Each cycle lasted 28 days. MM parameters were assessed at the end of each cycle. It was intended that the patients proceed to stem cell mobilization and autologous transplantation after 4 cycles of therapy.ResultsThe median number of cycles administered was 3.5. The overall response was 68%. The regimen was well tolerated by the majority of the patients; only patient discontinued treatment because of toxicity.ConclusionWe conclude that a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone was tolerated well, with no unexpected toxicities. However the response rate, even using lenalidomide at 50 mg, was not superior to standard dosing of thalidomide or lenalidomide plus dexamethasone.     

自体造血干细胞移植治疗多发性骨髓瘤的现状与展望

自体骨髓移植治疗多发性骨髓瘤(MM)始于20世纪80年代.随着自体外周血干细胞移植替代骨髓移植,大大提高了自体造血干细胞移植治疗MM的可行性.多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗显著地提高MM患者治疗的反应率、完全缓解率、无事件生存和(或)总生存,而治疗反应程度与生存相关.自体造血干细胞移植在欧美国家已成为年轻、适合(年龄≤65岁、肾功能正常和一般状况良好)的MM患者的一线标准治疗.同时已证实美法仑200mg/m2是预处理的最佳方案.双次移植有可能进一步提高治疗反应、无事件生存和(或)总生存,特别是对首次移植后未获得非常好的部分缓解或接近完全缓解的患者.近10年来,随着免疫调节药物沙利度胺及其衍生物和蛋白酶体抑制剂硼替佐米等新型抗MM药物的应用.显著提高了化疗的反应率和缓解率.目前尚无证据显示新药可以替代自体造血干细胞移植,但这些药物在移植前后的应用,进一步提高了MM的疗效.     

自体造血干细胞移植治疗多发性骨髓瘤的现状与展望

 自体骨髓移植治疗多发性骨髓瘤（MM）始于20世纪80年代。随着自体外周血干细胞移植替代骨髓移植,大大提高了自体造血干细胞移植治疗MM的可行性。多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗显著地提高MM患者治疗的反应率、完全缓解率、无事件生存和（或）总生存,而治疗反应程度与生存相关。自体造血干细胞移植在欧美国家已成为年轻、适合（年龄≤65岁、肾功能正常和一般状况良好）的MM患者的一线标准治疗。同时已证实美法仑200 mg／m2是预处理的最佳方案。双次移植有可能进一步提高治疗反应、无事件生存和（或）总生存,特别是对首次移植后未获得非常好的部分缓解或接近完全缓解的患者。近10年来,随着免疫调节药物沙利度胺及其衍生物和蛋白酶体抑制剂硼替佐米等新型抗MM药物的应用,显著提高了化疗的反应率和缓解率。目前尚无证据显示新药可以替代自体造血干细胞移植,但这些药物在移植前后的应用,进一步提高了MM的疗效。     

Management of disease- and treatment-related complications in patients with multiple myeloma

Treatment of myeloma has dramatically changed after introduction of novel agents, such as thalidomide, lenalidomide and bortezomib, with a significant improvement in response rate and survival of patients with myeloma. For newly diagnosed patients not eligible for transplant, the standards of care are now considered melphalan and prednisone (MP) plus thalidomide and MP plus bortezomib. Ongoing randomized trials are evaluating lenalidomide plus MP and lenalidomide plus dexamethasone. For newly diagnosed patients eligible for transplant, new induction regimens included the combination of high-dose dexamethasone plus thalidomide, high-dose dexamethasone plus lenalidomide (RD) and high-dose dexamethasone plus bortezomib (VD). The combinations RD, VD and bortezomib plus pegylated-liposomal-doxorubicin have received the US Food and Drug Administration approval for the treatment of relapsed myeloma. Different efficacious regimens are therefore now available for patients with myeloma. Disease control leads to improvement of all myeloma-related complications (anemia, bone disease, immune dysfunction and renal impairment), but physicians should take into account the choice of the therapeutic strategy, the expected toxicity profile of each of these regimens, together with the patient’s biologic age and comorbidities. Supportive care is an essential part of myeloma therapy, both for the treatment of myeloma-related complications, together with anti-myeloma treatment, and for the management of treatment-emergent adverse events. This chapter will provide an overview of frequency and management of main complications related to the disease itself and to the use of new drugs in newly diagnosed and relapsed patients with myeloma.     

Bortezomib,thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

BACKGROUND:

This single‐center retrospective study determined the efficacy of bortezomib, thalidomide, and dexamethasone (BTD) as induction for patients with multiple myeloma (MM) who were eligible for autologous stem cell transplantation (ASCT).

METHODS:

Patients with symptomatic MM who had received BTD induction before stem cell collection at Winship Cancer Institute were included. BTD induction comprised up to 8 3‐week cycles of bortezomib 1.3 mg/m² on Days 1, 4, 8, and 11; thalidomide 100 mg daily; and dexamethasone 40 mg on Days 1 through 4 and Days 9 through 12. Stem cell mobilization involved granulocyte‐colony–stimulating factor and/or cyclophosphamide. Response was assessed according to European Group for Blood and Marrow Transplantation criteria.

RESULTS:

Review of medical records identified 44 eligible patients (34 patients who were treated in the front‐line setting and 10 patients who were treated for recurrent disease) who received a median of 4 BTD cycles. The overall response rate (ORR) was 91%, which included a greater than or equal to very good partial response (≥VGPR) rate of 57% (including 20% stringent complete responses/complete response [sCR/CR] rate). In front‐line patients, the ORR was 94%, which included a 56% ≥VGPR rate (24% sCR/CR). The median CD34‐positive stem cell collection was 10.67 × 10⁶/kg. The ORR after ASCT in 34 patients who were evaluable for response was 100%, including a 76% ≥VGPR rate (53% sCR/CR). Among all 44 patients, the median progression‐free survival (PFS) was 27.4 months. The median overall survival (OS) was not reached after a median follow‐up of 25 months, and the 2‐year OS rate was 82%. There were no significant differences in PFS (27.4 months vs 23.5 months) or in 2‐year survival (80% vs 90%) between patients who did and did not undergo ASCT, respectively. Twenty patients (45%) developed neuropathy, including 4 (9%) with grade 3 neuropathy episodes, and 1 patient developed deep vein thrombosis.

CONCLUSIONS:

BTD was highly effective and well tolerated as induction for MM patients who were eligible for ASCT. Long‐term outcomes appeared to be similar with or without ASCT consolidation. Cancer 2010. © 2010 American Cancer Society.     

初发多发性骨髓瘤的治疗进展

多发性骨髓瘤（MM）是一种恶性浆细胞肿瘤。MM患者大多数年龄超过65岁,目前认为65岁以下初发MM患者的标准治疗为大剂量美法仑化疗支持的自体干细胞移植（ASCT）,而65岁以上老年MM患者的标准治疗至今仍认为是口服美法仑和泼尼松（MP）方案。但是一些新药的发明,如沙利度胺、雷利度胺和蛋白酶体抑制剂硼替佐米,能针对骨髓瘤细胞和骨髓微环境进行靶向治疗,联合使用在很大程度上能提高以往化疗方案的临床疗效。