多发性骨髓瘤维持治疗的研究进展

多发性骨髓瘤(multiple mfeloma,MM)是第二常见的血液肿瘤病,目前仍无法治愈。诱导治疗后序贯自体干细胞移植（ASCT）已经成为一种标准化治疗,但依然可能存在复发。使用维持治疗的目的是通过增加无进展生存期（PFS）,加深缓解,进而增加总生存期(OS)。本文主要对新药时代MM的维持治疗的进展作一综述。     

RVD方案对新诊断多发性骨髓瘤患者缓解深度的研究

  目的  分析来那度胺、硼替佐米及地塞米松(lenalidomide,bortezomib and dexamethasone,RVD)方案治疗新诊断多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者的疗效和安全性。  方法  回顾性分析2015年1月至2019年5月首都医科大学附属北京朝阳医院收治的48例NDMM患者,统计其临床特征及治疗疗效。  结果  48例患者的中位年龄为59(34~79)岁,DurieSalmon分期Ⅲ期患者44例;ISS分期Ⅱ期患者15例,Ⅲ期患者19例,12例伴浆细胞瘤,细胞遗传学高危患者占32.5%。全部患者接受RVD方案化疗,中位4(1~9)个周期,总有效率97.9%,完全缓解(complete response,CR)率为35.4%,4个周期较2个周期化疗后非常好的部分缓解(very good partial response,VGPR)以上疗效提高为(84.6% vs.64.1%);平均采集CD34+细胞数4.2(±2.6)×106/kg;诱导治疗后下一代流式微小残留病变(minimal residual disease,MRD)阴性率为20.6%,其中2例移植前MRD阳性者在移植后MRD转阴。治疗过程中2例发生3~4级血液学毒性,未发生3级以上非血液学不良事件。  结论  采用RVD方案治疗NDMM患者4个疗程,缓解率高,不良反应可耐受,且不影响干细胞采集。RVD诱导联合自体造血干细胞移植可进一步提高MRD阴性率。      

来那度胺为主的联合化疗方案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(lenalidomide)为主的联合化疗方案治疗复发难治性多发性骨髓瘤(multiple myeloma,MM)的临床疗效及不良反应.[方法]22例复发难治性MM患者中,来那度胺联合马法兰和地塞米松治疗者14例,来那度胺联合地塞米松治疗者7例,来那度胺联合亚砷酸和地塞米松治疗者1例.所有患者于2个疗程后评价疗效及不良反应.[结果] 22例患者中完全缓解(CR)2例(9.1％);非常好的部分缓解(VGPR)5例(22.7％);部分缓解(PR)12例(54.5％);无效以及死亡3例(13.7％),总有效率为86.3％.不良反应主要包括中性粒细胞减少(54.5％)、血小板减少(72.7％)、乏力(100％)以及继发感染(36.4％).[结论]以来那度胺为主的联合化疗是治疗复发难治性MM的合适治疗方案,近期疗效显著,患者耐受性好.     

新药治疗复发难治性多发性骨髓瘤的研究进展

复发难治性多发性骨髓瘤（MM）是血液系统恶性肿瘤治疗的难点.由于耐药现象的广泛存在,复发难治性MM治疗方案的选择较初治者有着更多影响因素,且疗效较差.文章分别评价了沙利度胺、来那度胺、硼替佐米等新药治疗复发难治性MM的单药及联合用药的疗效及相关不良反应,并报道了正在进行研究的新药的临床试验结果.     

65岁以上老年多发性骨髓瘤初治的化疗进展

多发性骨髓瘤（multiple myeloma,MM）是以骨髓单克隆浆细胞增多为特征的B细胞恶性肿瘤。对于老年（65岁以上）多发性骨髓瘤初治一般采用马法兰加泼尼松（MP）方案治疗,但其总的缓解率及生存率低。近几年来一些新的化疗药物对多发性骨髓瘤初治的疗效得到了肯定。本文就老年多发性骨髓瘤初治的化疗新进展作一综述。     

65岁以上老年多发性骨髓瘤初治的化疗进展

多发性骨髓瘤(multiple myeloma,MM)是以骨髓单克隆浆细胞增多为特征的B细胞恶性肿瘤。对于老年(65岁以上)多发性骨髓瘤初治一般采用马法兰加泼尼松(MP)方案治疗,但其总的缓解率及生存率低。近几年来一些新的化疗药物对多发性骨髓瘤初治的疗效得到了肯定。本文就老年多发性骨髓瘤初治的化疗新进展作一综述。     

来那度胺联合硼替佐米和地塞米松治疗多发性骨髓瘤的疗效观察

目的 探讨来那度胺联合硼替佐米和地塞米松治疗多发性骨髓瘤的疗效观察。方法 选取2016年1月至2020年1月间西电集团医院收治的80例多发性骨髓瘤患者,采用双盲法抽签分为观察组和对照组,每组40例。对照组患者采用硼替佐米+地塞米松治疗,观察组患者在对照组基础上联合来那度胺治疗,比较两组患者治疗前后的血清钙磷水平、细胞免疫功能及血液指标。结果 治疗后,两组患者血清钙和磷水平均下降,且观察组均低于对照组,差异均有统计学意义(均P<0.05)。治疗后,两组患者CD3⁺及CD4⁺指标均提升,且观察组高于对照组,两组患者CD8⁺指标均下降,且观察组低于对照组,差异均有统计学意义(均P<0.05)。治疗后,两组患者M蛋白和β₂微球蛋白水平均下降,且观察组低于对照组,差异均有统计学意义(均P<0.05)。结论 多发性骨髓瘤患者采用来那度胺联合硼替佐米、地塞米松治疗,可改善患者血清钙磷水平和血液指标,调节机体免疫功能。     

沙利度胺治疗难治性复发性多发性骨髓瘤的临床研究

目的：观察沙利度胺(Thalidomide，国内商品名：反应停)单药或联合地塞米松治疗多发性骨髓瘤(Multiple Myeloma，MM)的疗效及副作用。方法：单药组：男性13例，女性2例，中位年龄58岁。其中2例为初发的MM；1例为原发性浆细胞白血病(PCL)；12例为难治性MM，其中3例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停治疗起始剂量为100mg／d，根据患者耐受情况，逐渐加量，最高达800mg／d。联合组：男性20例，女性7例，中位年龄56岁。其中初发1例；1例为原发性PCL；25例为难治MM，其中2例为自体外周血干细胞移植(AutoPBSCT)术后复发。反应停剂量为400mg／d左右加用地塞米松40mg／天，第1～4天，第9～12天，第17～20天，1个月为一个疗程。结果：单药组42．9％(6／14)的患者对治疗有效，其中3例为完全缓解(CR)或接近完全缓解(Near-CR)，1例有明显治疗反应(Major response)，1例为部分缓解(PR)。12例难治性MM中4例有效(33．3％)；联合组有效率为57．7％(15／26)，其中4例为CR或Near-CR，2例有明显治疗反应，9例为PR。25例难治性MM中11例有效(44．0％)。两组间在总有效率及难治病例的有效率方面均无显著差异。两组患者均出现不同程度的便秘、皮疹等副作用，但均可耐受。结论：沙利度胺单药或联合地塞米松对难治性复发性MM均有效。     

靶向新药时代自体造血干细胞移植在多发性骨髓瘤治疗中的作用

多发性骨髓瘤（MM）是浆细胞恶性克隆性疾病,自体干细胞移植（ASCT）的加入,增加了大剂量化疗在MM治疗中的优势,使部分患者达到长期生存.即使在靶向新药时代ASCT仍可以明显提高治疗的反应率.靶向新药在ASCT前后联合应用,可辅助提高ASCT的疗效,这是目前使用靶向新药的趋势,但其仍不能取代ASCT在MM治疗中的地位.研究更为合理、有效、低毒的治疗方案是今后的方向.     

沙利度胺联合VAD方案治疗多发性骨髓瘤

目的评价沙利度胺治疗多发性骨髓瘤的治疗效果。方法采用配对观察的方法观察沙利度胺治疗多发性骨髓瘤的效果。将骨髓瘤患者随机分成A、B两组：A组采用沙利度胺＋VAD,使用剂量为沙利度胺200mg口服d1-21＋VAD方案（长春新碱0.5mg/d,d1-4,阿霉素10mg/d,d1-4;地塞米松40mg/d,d1-4、d9-12、d17-20）。B组只采用VAD方案,方案同上。结果A组治疗有效率明显高于B组。结论沙利度胺对多发性骨髓瘤治疗有明显的促进作用。     

The evolving role of maintenance therapy following autologous stem cell transplantation in multiple myeloma

ABSTRACT

Introduction: Maintenance therapy after autologous transplantation is a standard of care in newly diagnosed myeloma. However, there is no universal answer to the question of which maintenance strategy should be pursued after ASCT?

Areas covered: We conducted a MEDLINE search using the medical subject headings ‘multiple myeloma’, ‘autologous transplantation’ and ‘maintenance’ to identify available data from clinical trials on the role of different maintenance strategies after autologous transplantation for the newly diagnosed disease.

Expert opinion: A large meta-analysis demonstrated that lenalidomide prolongs progression-free and overall survival after autologous transplantation compared to observation/placebo. Further trials confirmed that lenalidomide maintenance increases rates of high-quality responses and one study demonstrated that lenalidomide maintenance improves outcomes regardless of cytogenetic risk. Although lenalidomide can cause side effects and is associated with an increased risk of second primary malignancies, its benefits outweigh the mentioned risks. The proteasome inhibitors ixazomib and bortezomib may partially overcome the negative effects of high-risk cytogenetics. Future trials will combine different agents and monoclonal antibodies during maintenance and will investigate whether minimal residual disease status can guide maintenance duration.     

Thromboembolic events with lenalidomide-based therapy for multiple myeloma

BACKGROUND: The purpose was to evaluate the incidence and risk factors of thromboembolism associated with lenalidomide therapy in newly diagnosed myeloma. METHODS: A pooled analysis was performed of patients with previously untreated multiple myeloma enrolled in clinical trials of lenalidomide-based therapy at the Mayo Clinic, Rochester, Minnesota, and the Italian Myeloma Network, Italy. The incidence of thrombosis, the effect of risk factors such as steroid dose and erythropoietin supplementation, and the effect of prophylaxis were examined. RESULTS: In all, 125 patients enrolled in 3 clinical trials were identified. Patients were stratified based on the concomitant corticosteroid dose. Fifty-two patients were in the high-dose group (dexamethasone 40 mg, 12 days a month); 73 patients were in the low-dose group (prednisone at any dose; or dexamethasone 40 mg, 4 days a month). A total of 110 patients were initiated on thromboprophylaxis; of these, 104 patients (95%) received aspirin. Ten patients (8%) developed deep vein thrombosis, including 4 who were not receiving any thromboprophylaxis at the time of the event. The rate of thromboembolic events was not different between patients who received concomitant erythropoietin therapy and those who did not, 4.8% and 8.6%, respectively (P= .54). A higher number of venous thrombotic episodes occurred in the high-dose corticosteroid group compared with the low-dose corticosteroid therapy group (12% vs 6%), but the difference was not statistically significant (P= .3). CONCLUSIONS: The incidence of deep vein thrombosis is lower than previously reported in the literature. There was a trend to a higher incidence of thrombosis in patients receiving high-dose corticosteroid therapy.     

Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone

BACKGROUND:

In the era of novel agents such as lenalidomide and bortezomib, risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches in patients with multiple myeloma (MM).

METHODS:

The authors analyzed the prognostic value of deletion del(13q14), del(17p13), +1q21, translocation t(4;14), t(11;14), and t(14;16) by fluorescence in situ hybridization (FISH) in a series of 92 patients with recurrent MM who were treated with lenalidomide and dexamethasone (len/dex) at the study center.

RESULTS:

Patients carrying del(13q14) or t(14;16) were found to have a shorter median time to disease progression (TTP) of 5.1 months (vs 14.4 months; P = .009) and 2.0 months (vs 10.5 months; P <.001), respectively. However, no effect on TTP was observed in patients harboring del(13q14) as an exclusive chromosomal aberration without the concomitant presence of t(4;14) or del(17p13). The median overall survival (OS) for patients with del(17p13) or +1q21 was 6.7 months (P = .002) and 8.3 months (P < .001), respectively, whereas the median OS for patients carrying none of these abnormalities was not reached. Multivariate analysis revealed that the effects of del(17p13) and +1q21 on OS were independent of patient age as well as the type and number of regimens administered before len/dex.

CONCLUSIONS:

The results of the current study suggest that the prognostic significance of t(4;14) may be ameliorated or eliminated in patients treated with len/dex, whereas the presence of del(17p13) or +1q21 is still associated with a dismal OS. The presence of t(11;14) and del(13q14) as exclusive chromosomal aberrations indicates no impact on outcome. Because of its rarity in MM, a confirmation of the prognostic role of the t(14;16) aberration is still pending. Cancer 2011. © 2010 American Cancer Society.     

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed.     

Lenalidomide and its role in the management of multiple myeloma

Treatment of multiple myeloma has changed in recent years. Advances in the understanding of the pathogenesis of the disease and the mechanism of drug resistance have led to the development of novel effective biological treatment agents such as thalidomide and bortezomib. Lenalidomide is an oral analogue of thalidomide that lacks the neurotoxic side effects associated with the parent drug, and has shown significant antimyeloma activity. Lenalidomide has now been approved by the US FDA and the European Medicines Agency for use in combination with dexamethasone in patients with at least one prior therapy. Several trials are testing lenalidomide-based regimens in both newly diagnosed and relapsed patients. This review summarizes the profile of lenalidomide and its current role in the treatment of multiple myeloma.     

Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma

BACKGROUND:

Early versus delayed autologous stem cell transplantation (SCT) results in comparable overall survival in patients with multiple myeloma (MM) who receive alkylator‐based therapies. It is not clear whether this paradigm holds true in the context of new therapies, such as immunomodulatory drugs (IMiDs).

METHODS:

The authors studied 290 patients with untreated MM who received IMiD‐based initial therapy, including 123 patients who received thalidomide‐dexamethasone (TD) and 167 patients who received lenalidomide‐dexamethasone (LD) induction before SCT. Patients who underwent a stem cell harvest attempt were considered transplantation‐eligible and were included. SCT within 12 months of diagnosis and within 2 months of harvest were considered early SCT (n = 173; 60%). SCT >12 months after diagnosis was considered delayed SCT (n = 112; 40%).

RESULTS:

In the delayed SCT group, 42 patients had undergone SCT at the time of the current report, and the median estimated time to SCT was 5.3 months and 44.5 months in the early SCT and delayed SCT groups, respectively. The 4‐year overall survival rate from diagnosis was 73% in both groups (P = .3) and was comparable in those who received TD (68% vs 64%, respectively) and those who received LD (82% vs 86%, respectively) as initial therapy. The time to progression after SCT was similar between the early and delayed SCT groups (20 months vs 16 months; P value nonsignificant).

CONCLUSIONS:

The current results indicated that, in transplantation‐eligible patients who receive IMiDs as initial therapy followed by early stem cell mobilization, delayed SCT results in similar overall survival compared with early SCT. It is noteworthy that an excellent 4‐year survival rate of >80% was observed among transplantation‐eligible patients who received initial therapy with LD regardless of the timing of transplantation. Cancer 2011;. © 2011 American Cancer Society.