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.     

沙利度胺联合VAD方案治疗多发性骨髓瘤的疗效及对患者免疫功能的影响

目的 研究沙利度胺联合VAD方案治疗多发性骨髓瘤的疗效及对患者免疫功能的影响.方法 选取74例多发性骨髓瘤患者,根据分层随机分组法分为观察组和对照组,每组各37例.对照组采取VAD方案进行治疗,观察组在此基础上加以沙利度胺进行治疗.分析两组患者治疗前和治疗4个周期后免疫功能、骨髓瘤细胞、β2-微球蛋白、M蛋白、血红蛋白指标变化,比较两组患者的临床疗效和不良反应.结果 治疗4个周期后,观察组的CD4+CD25+、IL-6、TGF-β指标明显低于对照组,INF-γ/IL-10指标高于对照组,差异均有统计学意义(P<0.05).治疗4个周期后,观察组的骨髓瘤细胞、β2-微球蛋白、M蛋白指标明显低于对照组,血红蛋白明显高于对照组,差异均有统计学意义(P<0.01).观察组总有效率高于对照组(P<0.05).观察组和对照组的皮疹、感染、便秘、嗜睡等不良反应发生率比较差异无统计学意义(P>0.05).结论 在治疗多发性骨髓瘤中采取沙利度胺联合VAD方案能有效改善患者的免疫功能,临床疗效较好,不良反应属于轻度型,患者均可耐受.     

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.     

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post‐transplant results. Therefore, best frontline treatment for transplant‐eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta‐analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide‐lenalidomide‐dexamethasone) over TD‐based (thalidomide‐dexamethasone, HR = 0.76,0.62‐0.90), VAD‐based (HR = 0.71,0.52‐0.90), and Z‐Dex (idarubicin‐dexamethasone, HR = 0.37,0.17‐0.76) regimens. Concerning PFS, VTD (bortezomib‐thalidomide‐dexametasone) showed superior results when compared with TD‐based (HR = 0.66,0.51‐0.84), VAD‐based (HR = 0.61,0.46‐0.82), Z‐Dex (HR = 0.42,0.22‐0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41‐0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide‐only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide‐doxorubicin‐dexamethasone), neurological with PAD (bortezomib‐doxorubicin‐dexamethasone), infectious with Dex, hematological with Z‐Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant‐eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression‐free survival, when compared with bortezomib/thalidomide protocols.     

Postrelapse survival rate correlates with first‐line treatment strategy with thalidomide in patients with newly diagnosed multiple myeloma: a meta‐analysis

To define whether or not thalidomide exposure upfront to newly diagnosed patients with multiple myeloma would adversely impact postrelapse survival (PRS), we performed a meta‐analysis of randomized controlled trials. Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched. Thirteen trials were identified, covering a total of 6097 subjects, and PRS data were available from eight trials. The summary hazard ratio (thalidomide vs control) of all those trials for PRS was 1.23 [95% CI, 1.05–1.45]. The HRs of thalidomide maintenance subgroups were 0.90 [0.57–1.41] for PRS, 0.61 [0.44–0.83] for progression‐free survival ( PFS) and 0.54 [0.36–0.80] for overall survival, respectively. The corresponding ratios of thalidomide induction and maintenance subgroups were 1.41 [1.13–1.76] for PRS, 0.68 [0.59–0.79] for PFS and 0.87 [0.73–1.04] for overall survival, respectively. In conclusion, thalidomide exposed upfront correlated with shorter PRS that partially compensated for prolonged initially PFS and resulted in no survival benefit when it is given as both induction pre‐autologous and maintenance post‐autologous stem cell transplantation; shorter PRS was not observed, and survival was improved when it is given only during maintenance phase following autologous stem cell transplantation in the patients with myeloma and who are eligible for transplant. Copyright © 2011 John Wiley & Sons, Ltd.     

沙利度胺联合改良VAD方案治疗多发性骨髓瘤临床疗效观察

目的:观察沙利度胺联合改良VAD方案治疗多发性骨髓瘤（MM）的临床疗效和不良反应。方法:MM患者79例,均给予沙利度胺联合改良VAD方案治疗。结果:第1疗程后79例患者中CR为12.66%（10/79）,总有效率为77.22%（61/79）;3疗程后79例患者中CR为40.51%（32/79）,总有效率为83.54%（66/79）。44例大于等于60岁患者中,CR为40.91%（18/44）,总有效率为84.09%（37/44）。35例小于60岁患者中CR为40%（14/35）,总有效率为85.71%（30/35）,两组患者经统计学检验临床疗效无显著性差异（P>0.05）。38例IgG型患者中CR为44.74%（17/38）,总有效率为92.11%（35/38）。23例IgA型患者中CR为39.13%（9/23）,总有效率为82.61%（19/23）。8例轻链型患者中CR为37.50%（3/8）,总有效率为75.00%（6/8）。10例不分泌型患者中CR为30.00%（3/10）,总有效率为70%（7/10）;各组患者经统计学检验临床疗效无显著性差异（P>0.05）。结论:沙利度胺联合改良VAD化疗方案治疗MM完全缓解率及总有效率高,对不同分型及年龄组患者疗效均显著,值得进一步临床观察和推广。     

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。     

PAD序贯自体造血干细胞移植治疗难治多发性骨髓瘤(附22例)

目的:多发性骨髓瘤(multiple myeloma,MM)至今仍不可治愈,几乎所有病人均会出现复发或难治,本文初步探讨硼替佐米应用于难治性MM患者PAD化疗并序贯自体外周血造血干细胞移植(autologous pe-ripheral blood stem cell t ransplantation,APBSCT)的可行性和疗效。方法:采用PAD(硼替佐米+阿霉素+地塞米松)方案治疗复发或难治性MM。结果:22例中3例难治MM患者给予PAD方案化疗4-6个疗程后,2例达到接近完全缓解(nCR),1例达到部分缓解(VGPR),并随后行APBSCT,动员方案PAD+CTX(PAD,环磷酰胺1.5g/m2,d15)联合G-CSF。预处理方案为马法兰140mg/m2。移植后采用沙利度胺100mg/天。所有患者在移植前均达到CR或VGPR,干细胞采集充分,安全有效,移植后造血功能均快速顺利重建。无1例死亡。移植后采用沙利度胺维持,随访3-12个月,病情稳定。结论:PAD用于难治MM患者的治疗达CR后,继续序贯进行APBSCT不仅可行,而且PAD不影响正常造血干细胞动员,故采用PAD和序贯用PAD+CTX动员方案的APBSCT的治疗手段,为难治MM患者的治疗提供新的治疗手段。但对长期生存的改善作用需进一步研究。     

PAD序贯自体造血干细胞移植治疗难治多发性骨髓瘤（附22例）

目的：多发性骨髓瘤（multiple myeloma,MM）至今仍不可治愈,几乎所有病人均会出现复发或难治,本文初步探讨硼替佐米应用于难治性MM患者PAD化疗并序贯自体外周血造血干细胞移植（autologous pe-ripheral blood stem cell t ransplantation,APBSCT）的可行性和疗效。方法：采用PAD（硼替佐米＋阿霉素＋地塞米松）方案治疗复发或难治性MM。结果：22例中3例难治MM患者给予PAD方案化疗4-6个疗程后,2例达到接近完全缓解（nCR）,1例达到部分缓解（VGPR）,并随后行APBSCT,动员方案PAD＋CTX（PAD,环磷酰胺1.5g/m2,d15）联合G-CSF。预处理方案为马法兰140mg/m2。移植后采用沙利度胺100mg/天。所有患者在移植前均达到CR或VGPR,干细胞采集充分,安全有效,移植后造血功能均快速顺利重建。无1例死亡。移植后采用沙利度胺维持,随访3-12个月,病情稳定。结论：PAD用于难治MM患者的治疗达CR后,继续序贯进行APBSCT不仅可行,而且PAD不影响正常造血干细胞动员,故采用PAD和序贯用PAD＋CTX动员方案的APBSCT的治疗手段,为难治MM患者的治疗提供新的治疗手段。但对长期生存的改善作用需进一步研究。     

Polymorphism of IL‐10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib

Interleukin‐10 (IL‐10) and IL‐10 receptor (IL‐10R) single nucleotide polymorphisms have been implicated in the pathogenesis of many cancers. We investigated the influence of IL‐10 ?592C/A, IL‐10RA I224V, and IL‐10RB K47E on the risk of developing multiple myeloma (MM) and the clinical features of MM. We extracted the genomic DNA from 128 MM patients and 202 healthy controls and used polymerase chain reaction–restriction fragment length polymorphism method to detect IL‐10 promoter ?592C/A (rs1800872), IL‐10RA (rs2228055), and IL‐10RB K47E (rs2834167) genotypes. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment. No statistically significant difference was observed in the genotype and allele frequencies of IL‐10 ?592C/A, IL‐10RA I224V, and IL‐10RB K47E between MM patients and healthy controls. IL‐10RA II genotype was significantly associated with a hemoglobin level lower than that of IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs 10.3 ± 2.33 g/dL; P  = .021). IL‐10 ?592 AA genotype was significantly associated with OS better than that of CA and CC genotypes (median OS, 74.5 vs 46.3 months; P  = .047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and those treated with conventional treatments (median OS, 74.5 vs 38.2 months; P  = .021). Therefore, we also examined the effect of IL‐10 and IL‐10R polymorphisms on the clinical variables and OS of patients treated with thalidomide and/or bortezomib. In addition, IL‐10RB EE genotype was significantly associated with poorer survival than KK and KE genotypes (median OS, 46.3 vs 78.8 months; P  = .015). Our findings indicate that IL‐10 and IL‐10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL‐10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib.     

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.     

酞咪哌啶酮联合化疗初治多发性骨髓瘤疗效观察

目的:探讨酞咪哌啶酮(thalidomide,商品名反应停)联合化疗初治多发性骨髓瘤(multiplemyeloma,MM)的初步疗效。方法:治疗组14例初治多发性骨髓瘤应用反应停起始剂量100mg/d~200mg/d,每2周增加100mg~200mg直到患者能够耐受,最大剂量不超过600mg/d,同时联合以马法兰为主的MP或M2方案化疗;对照组20例初治多发性骨髓瘤单用MP或M2方案化疗。观察比较两组的3个月有效率、1年无事件生存率(EFS)和2年总生存率(OS)。结果:有效(部分缓解加进步)率治疗组为85.7%,对照组为50%。1年EFS治疗组为71.4%,对照组为35%。2年OS治疗组为57.1%,对照组为25%。反应停治疗组副作用可以耐受,便秘最常见。结论:反应停联合化疗可提高初治MM的疗效和1年EFS、2年OS。     

新药时代自体造血干细胞移植在多发性骨髓瘤中的应用前景*

自体干细胞移植（ASC T）在传统化疗时代已成为65岁以下初诊多发性骨髓瘤（MM）的标准一线治疗。随着新型靶向药物为基础的化疗在诱导、巩固和维持治疗阶段的广泛应用,MM的缓解率得到显著提高,因此是否需要ASCT成为了新药时代关注的焦点。目前现有的资料仍然支持ASCT是符合条件的初诊MM患者的一线治疗,新药作为ASCT前诱导治疗以及ASCT后巩固、维持治疗有助于进一步提高缓解率,延长无进展生存时间。但今后仍需要开展更多前瞻性临床试验进一步明确ASCT在MM中的作用、进一步优化治疗方案,以期实现MM治愈的目标。     

Interferon-alpha as maintenance therapy in patients with multiple myeloma.

BACKGROUND: The effect of interferon-alpha 2b (IFN-alpha-2b) on progression-free and overall survival as well as quality of life (QoL) was studied in mainly elderly patients with multiple myeloma (MM), who reached a plateau phase after melphalan/prednisone induction. PATIENTS AND METHODS: In an open phase III trial, 262 patients, median age 69 years (range 34-91), received at least 10 monthly courses of melphalan/prednisone followed by response evaluation. Plateau phase was reached by 128 patients. Next, 90 patients were randomized between IFN-alpha-2b and no maintenance therapy. Reasons for non-randomization were: refusal (18), concomitant disease (nine), protocol violation (six), WHO performance status >2 (four) and allogeneic transplantation (one) RESULTS: At a median follow-up from diagnosis of 97 months (0-140) for those patients alive, IFN-alpha-2b therapy was associated with improved progression-free survival (median 13.5 versus 8.4 months from randomization), although this did not translate in a better overall survival (41 versus 38.4 months). One-third of patients discontinued IFN-alpha due to toxicity. No differences were observed between patient groups in QoL. CONCLUSIONS: IFN maintenance therapy in MM prolongs progression-free survival and, provided that the burden of toxicity is not too high, does not adversely affect QoL.     

Autologous-allogeneic tandem stem cell transplantation in patients with multiple myeloma

The decrease in treatment-related mortality by using reduced intensity conditioning and the well-proven immunological effect of the graft to multiple myeloma cells has increased the interest in using allogeneic stem cell transplantation in patients with multiple myeloma. The concept of a cytoreductive autograft followed by a dose-reduced allogeneic stem cell transplantation appears to be the most promising approach. Preliminary reports of several groups observed a treatment-related mortality at 1 year ranged from 0 - 17%. The rate of acute graft-vs.-host disease (GvHD) grade II - IV ranged from 32 - 44% and of chronic GvHD from 28 - 64%. The overall response rates for all studies ranged from 68 - 83%, including a high rate of complete remissions of 52 - 83%. The overall survival at 2 or 3 years was between 62% and 78%, and the progression-free survival between 54% and 56%. Despite the high rate of complete remissions after autologous-allogeneic tandem transplantation observed in nearly all trials, the relapse rate is quite considerable and exceeded nearly 40% at 2 years. Therefore, the reduced allogeneic treatment approach in patients with multiple myeloma has still to be improved and further preclinical and clinical research is focused on two major issues: (i) to further reduce treatment-related mortality and (ii) to enhance the remission status after transplantation, via adoptive immunotherapy inducing molecular remission and enhancing the cure rate of this approach.     

Oral ixazomib maintenance therapy in multiple myeloma

Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib.     

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

BACKGROUND:

Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced‐intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long‐term outcome of RIC in the recurrent/refractory setting.

METHODS:

A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine‐melphalan based conditioning and stem cell grafts from a related (n = 27) or unrelated donor (n = 23).

RESULTS:

The median age was 53 years. Forty‐seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow‐up of 6.4 years (range, 5‐7.9 years), the overall and progression‐free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7‐year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome.

CONCLUSIONS:

Allogeneic SCT can result in long‐term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010. © 2010 American Cancer Society.     

An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma

The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%) responded to THAL with a mean response duration of 11.9 months (ranging from 1 to 48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64 patients (27.4% of the whole group), the response to THAL lasted > or =18 months with a mean response lasting 24 months. Statistical analysis of the group of nonresponders and patients with long-term response to THAL showed a significantly higher serum albumin level (P=0.0003) and haemoglobin level (P=0.05), as well as a lower beta2 microglobulin (beta2M) (P=0.022), LDH (P=0.045) serum level in patients with long-term response. In this study, the LDH and serum albumin level were predictors for response to THAL therapy. The beta2M serum level was not a predictor for response to THAL. The albumin serum level was the best parameter distinguishing the group of patients with long-term response to THAL from the entire responding group (P=0.02).     

Novel agents-based regimens as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis of randomized controlled trials

To investigate the effect of novel agents like bortezomib, lenalidomide and thalidomide as part of induction treatment prior to autologous stem-cell transplantation (ASCT) for previously untreated patients with multiple myeloma, we performed a meta-analysis of randomized controlled trials (RCTs). Medline, Embase, the Cochrane controlled trials register and the Science Citation Index were searched for RCTs of novel agents as part of induction therapy before ASCT. Three RCTs of bortezomib, two RCTs of thalidomide and no RCT of lenalidomide were identified, covering a total of 2,316 subjects. Due to different mechanisms of action, we performed a subgroup analysis by type of agent (thalidomide or bortezomib). The weighted risk ratios of a complete response (CR) were 4.25 [95% CI: 2.44-7.41] (p < 0.001) for bortezomib and 1.66 [95% CI: 1.15-2.38] (p = 0.007) for thalidomide, respectively. The summary hazard ratios for progression-free survival (PFS) were 0.73 [95% CI: 0.59-0.89] (p = 0.002) for bortezomib and 0.68 [95% CI: 0.59-0.79] (p < 0.001) for thalidomide, respectively. The corresponding ratios for overall survival (OS) were 0.87 [95% CI: 0.64-1.18] (p = 0.37) and 0.88 [95% CI: 0.73-1.05] (p = 0.14), respectively. Additionally, there was a statistically significant heterogeneity between subgroups (thalidomide and bortezomib) for CR (p = 0.005) but nonsignificant for PFS (p = 0.64) and OS (p = 0.97). In conclusion, our analysis showed novel agents as induction treatment prior to ASCT improved CR and PFS but not OS.