Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese,multicenter, phase 1/2, safety and efficacy study

Isatuximab, an anti‐CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open‐label, single‐arm, multicenter, phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent cycles. Cohort 1 (n = 3) received 10 mg/kg QW/Q2W; cohort 2 (n = 5) received 20 mg/kg QW/Q2W. No dose‐limiting toxicities occurred; the recommended dose for the single‐arm phase 2 study (n = 28) was 20 mg/kg QW/Q2W. The overall safety profile was consistent with the current knowledge of isatuximab. The most common adverse events were infusion reactions (42.9%; 12/28); all were grade 1/2 and generally occurred during the first infusion. The overall response rate with 20 mg/kg QW/Q2W isatuximab was 36.4% (12/33); patients with high‐risk cytogenetic abnormalities had comparable results. In phase 2, the median progression‐free survival was 4.7 (95% confidence interval, 3.75 to not reached) months. Median overall survival was not reached. Isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM including high‐risk cytogenetic patients. This trial is registered at ClinicalTrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT02812706","term_id":"NCT02812706"}}NCT02812706.     

Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma

Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM.     

Use of depth of response to predict progression‐free survival in relapsed or refractory multiple myeloma: Evaluation of results from 102 clinical trials

Progression‐free survival (PFS) is the standard endpoint for demonstration of clinical effectiveness of novel therapies in relapsed or refractory multiple myeloma (RRMM). However, the long evaluation times for PFS limits its usefulness in the development of new therapies. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in RRMM. A database was systematically developed from 268 identified RRMM trials reported from 1999 to 2016. Evaluated covariates for the relationship between response rates and PFS included age, sex, drug class(es), and number of drug classes. One‐hundred two (102) trials involving 136 cohorts were included in the meta‐analysis, representing 13 322 patients in total. Regression analysis using response rates and median PFS indicated that the correlation between very good partial response (VGPR) or better and median PFS was higher (R² = 0.63) than the separately analyzed correlations between clinical benefit, overall response, or complete response rate and median PFS (R² = 0.47 – 0.52). Subsequent covariate analysis revealed that treatment with an immunomodulatory imide drug (IMiD) further improved the relationship (R² = 0.69), with a longer median PFS at a given VGPR or better rate when at least 1 drug treatment was an IMiD. Number of drug classes was not found to alter this relationship. In conclusion, VGPR or better rate can be used to predict the median PFS, with adjustment for the additional PFS provided by an IMiD.     

Efficacy and tolerability of bendamustine,bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with ⩽4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1–2 prior therapies and 33% were refractory to the last treatment. The response rate⩾partial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.     

Weekly treatment with bortezomib for patients with recurrent or refractory multiple myeloma: a phase 2 trial of the Minnie Pearl Cancer Research Network

BACKGROUND: The purpose of the current study was to evaluate the efficacy and toxicity of weekly bortezomib in the treatment of patients with recurrent/refractory multiple myeloma. METHODS: A total of 40 patients with multiple myeloma who had received either 1 or 2 previous treatment regimens were treated with bortezomib at a dose of 1.6 mg/m(2) intravenously for 4 consecutive weeks, followed by 1 week without treatment. Responses were measured using International Myeloma Working Group criteria. RESULTS: Twenty-two patients (55%; 95% confidence interval, 40%-70%) achieved objective responses to treatment, with a median response duration of 16 months. The median progression-free survival for all patients was 9.6 months, with a 1-year progression-free survival rate of 39%. The 1-year and 2-year overall survival rates were 75% and 51%, respectively. Weekly bortezomib was generally well tolerated; grade 3/4 (using the National Cancer Institute Common Toxicity Criteria [version 3.0]) neutropenia (13%), thrombocytopenia (20%), fatigue (15%), diarrhea (13%), and neuropathy (10%) were experienced by a minority of patients. CONCLUSIONS: In the current study, a schedule of weekly bortezomib was found to be effective and well tolerated in patients with previously treated multiple myeloma. Although the response rate and duration appear comparable to those achieved with twice-weekly bortezomib, the relative efficacy of these 2 schedules cannot be determined definitively on the basis of this phase 2 study. A weekly schedule of bortezomib is a reasonable option for patients who have logistic difficulties receiving a twice-weekly schedule, and is an attractive schedule for incorporation into combination regimens.     

Pharmacokinetic study of bortezomib administered intravenously in Taiwanese patients with multiple myeloma

This phase 4, single‐arm, non‐randomized, open‐label, post approval commitment study evaluated the pharmacokinetics and safety of bortezomib in Taiwanese patients with multiple myeloma. Patients (≥20 years) with measurable secretory multiple myeloma (serum monoclonal IgG ≥10, IgA/IgE ≥5, IgD ≥0.5 g/L, IgM present [regardless of level], and urine M protein of ≥200 mg/24 h) received intravenous bortezomib 1.3 mg/m², twice weekly for 2 weeks, followed by a 10‐day resting phase (days 12 to 21). Pharmacokinetics and safety were assessed at pre‐specified time points. All enrolled patients (n = 18, men: 11; women: 7) completed the study. Mean (SD) C_max (maximum observed plasma concentration) on day 11 was 266 (77.5) ng/mL, approximately 60% higher compared with non‐Asian patients receiving a similar bortezomib regimen but with overlapping ranges. Because of the protracted terminal phase, half‐life (t_1/2), area under the plasma concentration‐time curve from time 0 to infinity (AUC_∞), volume of distribution (V_z), and systemic clearance were not assessable. All patients experienced treatment‐emergent adverse events (TEAEs); 78% were drug‐related. Most commonly reported TEAEs were thrombocytopenia (n = 11 [61%]), neutropenia (n = 9 [50%]), leukopenia (n = 6 [33%]), and diarrhoea (n = 6 [33%]); the most common serious adverse event was pneumonia (n = 2 [11%]). One patient had a dose reduction due to a TEAE of thrombocytopenia. Overall, bortezomib exposure (AUC) in Taiwanese patients (AUC_last [SD]: 230 [147] ng·h/mL) with twice weekly intravenous administration was comparable with non‐Asian population (AUC_last [SD]: 241 [82] ng·h/mL). Bortezomib treatment was associated with manageable toxicity profile and did not limit the continuity of therapy.     

A phase II multicenter study of troxacitabine in relapsed or refractory lymphoproliferative neoplasms or multiple myeloma

Options for patients with relapsed/refractory lymphoproliferative disorders and multiple myeloma are currently limited. Troxacitabine has shown promise in preclinical studies in a variety of malignancies; hence, the current study was conducted to evaluate the activity of troxacitabine in relapsed or refractory lymphoid malignancies. This was a phase II, open-label, multinational, multicenter study of patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. Thirty-four adults were enrolled in the study and received the study drug at either 5.4 mg/m² (n = 16) or 4.3 mg/m² (n = 18). The dose was decided in a phase I study, during which dose escalation was carried to reach a maximum tolerated dose with an acceptable toxicity profile. Two separate phase I studies were performed in Europe and the US. Troxacitabine was administered by intravenous infusion over 30 min daily for days 1 - 5 every 4 weeks. Treatment was continued to disease progression or until the subjects met criteria for withdrawal or unacceptable toxicities were evident as outlined in the protocol. Two patients had a partial response (PR) to treatment with troxacitabine to yield an overall response rate of 13%. There were no complete responses seen with the drug. Stable disease was achieved in 15 patients (44%). All patients had at least one treatment related adverse event, which led to six withdrawals from the study. Hematologic toxicity constituted the most common adverse events. Serious adverse effects were seen in 62% of patients. None of the 13 deaths were attributed directly to troxacitabine. As a single agent, troxacitabine has limited benefit in patients with advanced lymphoproliferative disorders or multiple myeloma. Future studies will be needed to address modified dosing according to emerging pharmacokinetic and pharmacodynamic data and combination therapy which may lead to improved clinical benefit for troxacitabine in hematologic malignancies.     

Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone

BACKGROUND: Recent studies have demonstrated synergy between bortezomib and a number of conventional cytotoxic agents. This study examined whether or not the speed of the response, progression and safety from a combination treatment of bortezomib with common chemotherapeutic drugs is superior to bortezomib monotherapy. METHODS: Fifty-seven patients with relapsed, refractory multiple myeloma (MM) who had received at least two cycles of treatment including bortezomib were enrolled in this study. The median age was 56 (35-79) years and 49.1% were male. Thirty-two patients were treated with bortezomib alone and 25 were treated with chemotherapeutic agents that were given in combination with bortezomib. The monoclonal immunoglobulin (mIg) or free light chain (FLC) concentrations were determined in the sera before and after two cycles of bortezomib treatment. The adverse events were assessed and graded according to the NCI Common Toxicity Criteria (version 2.0). RESULTS: Thirty-one of the 57 patients (54.4%) attained an early objective response (EOR) after the second bortezomib treatment, defined as a >/=50% decrease in the serum mIg or FLC concentration. Improvements in the response were observed when common chemotherapeutic agents were added to bortezomib monotherapy. In patients who received bortezomib combined with chemotherapeutic agents, 19 out of 25 patients (76%) showed an EOR, whereas 12 out of 32 patients (37.5%) given bortezomib monotherapy achieved an EOR after the second cycle of bortezomib treatment (P = 0.004); the median decrease from the baseline in the paraprotein level was 74.6 +/- 5.9 and 39.7 +/- 4.2%, respectively (P = 0.003). A statistically significant elevation of serum lactic dehydrogenase (P = 0.007) and alkaline phosphatase (P = 0.027) from baseline within two cycles of bortezomib treatment was observed in responding patients. With the combination treatment, peripheral neuropathy of >/=Grade II occurred in 12 out of 25 patients (48%) compared with 12 of 32 (37.5%) in those given bortezomib alone (P = 0.589). The median time to progression of disease was similar in the two groups (359 +/- 43.5 versus 365 +/- 103.5, P = 0.688). The multivariate Cox regression model showed that a high serum albumin and low beta2-microglobulin are favorable factors for the progression-free survival following bortezomib treatment. CONCLUSIONS: Bortezomib in combination with common chemotherapeutic agents is more active in the treatment of relapsed, refractory MM than with bortezomib alone. However, more effective post-bortezomib treatment is needed to reduce the rate of disease progression particularly in patients with high tumor burden.     

Bortezomib,melphalan, and prednisone in elderly patients with relapsed/refractory multiple myeloma

BACKGROUND:

In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event‐free survival compared with MP alone.

METHODS:

In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose‐intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m² on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28‐day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled.

RESULTS:

After a median follow‐up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles.

CONCLUSIONS:

A weekly infusion of bortezomib associated with lower dose‐intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM. Cancer 2013. © 2012 American Cancer Society.     

A phase 2 study of estramustine,docetaxel, and bevacizumab in men with castrate‐resistant prostate cancer

BACKGROUND:

The use of docetaxel prolongs survival for patients with castrate‐resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC.

METHODS:

This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate‐specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression‐free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival.

RESULTS:

Seventy‐nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty‐three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty‐four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity.

CONCLUSIONS:

The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. Cancer 2011. © 2010 American Cancer Society.     

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma

A randomized phase II selection design study (JCOG0904) was carried out to evaluate the more promising regimen between bortezomib (Bor) plus dexamethasone (Dex; BD) and thalidomide (Thal) plus Dex (TD) in Bor and Thal‐naïve patients with relapsed or refractory multiple myeloma (RRMM). Patients ≥20 and <80 years old with a documented diagnosis of symptomatic multiple myeloma (MM) who received one or more prior therapies were randomized to receive BD (Bor 1.3 mg/m²) or TD (Thal 200 mg/d). In both arms, 8 cycles of induction (3‐week cycle) were followed by maintenance phase (5‐week cycle) until disease progression, unacceptable toxicity, or patient refusal. The primary end‐point was 1‐year progression‐free survival (PFS). Forty‐four patients were randomized and assigned to receive BD and TD (n = 22, each group). At a median follow‐up of 34.3 months, the 1‐year PFS in the BD and TD arms were 45.5% (95% confidence interval (CI), 24.4%‐64.3%) and 31.8% (95% CI, 14.2%‐51.1%), respectively, and the overall response rates were 77.3% and 40.9%, respectively. The 3‐year overall survival (OS) was 70.0% (95% CI, 44.9%‐85.4%) in the BD, and 48.8% (95% CI, 25.1%‐69.0%) in the TD arm. Among grade 3/4 adverse events, thrombocytopenia (54.5% vs 0.0%) and sensory peripheral neuropathy (22.7% vs 9.1%) were more frequent in BD when compared with the TD arm. Patients treated with BD had better outcomes than those treated with TD with regard to 1‐year PFS and 3‐year OS. Thus, BD was prioritized over TD for further investigations in Bor and Thal‐naïve RRMM patients. (Clinical trial registration no. UMIN000003135.)     

Carfilzomib monotherapy in Japanese patients with relapsed or refractory multiple myeloma: A phase 1/2 study

This multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m². Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m² carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m² group at this final analysis was 4.7 months (range: 0.3‐39.4). Overall response rate in the 20/27 mg/m² group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Median progression‐free survival and overall survival in the 20/27 mg/m² group were 5.1 months (95% CI, 2.8‐13.6) and 22.9 months (95% CI, 14.1‐not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m² group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients.     

皮下注射硼替佐米治疗多发性骨髓瘤研究进展

多发性骨髓瘤是以骨髓中克隆性浆细胞恶性增殖为特征的肿瘤。有硼替佐米参与的联合化疗大大改善了患者的预后。周围神经病变是其常见不良反应之一,严重的不良反应通常会导致需要减低用药剂量或停止治疗,影响了其在临床中的应用。将硼替佐米由传统静脉快速注射改为皮下注射并不影响临床疗效,且具有更好的安全性。皮下硼替佐米给药为MM患者提供了一种新的治疗选择方式,本文将对皮下注射硼替佐米治疗多发性骨髓瘤的研究进展作一综述。     

硼替佐米治疗多发性骨髓瘤的疗效

目的:观察硼替佐米治疗多发性骨髓瘤的疗效及不良反应。方法:多发性骨髓瘤患者26例,均给予以硼替佐米为基础的联合方案治疗,患者分别接受2-6个周期治疗。结果:26例患者在接受2个疗程硼替佐米治疗后,其中2例患者完全缓解,7例患者达非常好的部分缓解,16例患者部分缓解,1例患者出现疾病进展。不良反应主要有周围神经病变、血液学毒性、消化道症状以及感染等,经对症支持大部分可以缓解。结论:硼替佐米对于多发性骨髓瘤起效快,有一定程度不良反应,但大部分可逆转。     

Pooled analysis of the reports of pomalidomide after failure of lenalidomide and (or) bortezomib for multiple myeloma

The use of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma is not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the effectiveness of pomalidomide after failure of lenalidomide and (or) bortezomib. We searched published reports including pomalidomide, lenalidomide and (or) bortezomib. Seven reports were identified. Pomalidomide‐based regimen was pomalidomide plus low‐dose dexamethasone (POM + LoDEX). Six randomized controlled trials enrolling a total of 641 patients that evaluated the treatment effects of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma were included. Pooled results showed that the overall response rate (ORR) was 31% in the POM + LoDEX group. Analysis of heterogeneity showed very little (p = 0.997, I² = 0%), suggesting that response rates of POM + LoDEX therapy were consistent across those included trials. Stable disease was achieved in 40% of 603 patients (heterogeneity: p = 0.980, I² = 0%). In those >65 years, overall response was achieved in 32% of 71 patients (heterogeneity: p = 0.77, I² = 0%). POM + LoDEX showed promising activity in the 95 patients with high‐risk cytogenetic abnormalities: ORR was 27% (heterogeneity: p = 0.97, I² = 0%). In the pooled analysis, toxicity consisted primarily of myelosuppression: Grade 3 or 4 neutropenia was seen in 53% (heterogeneity: p = 0.857, I² = 0%). Pomalidomide may produce clinical benefits in patients who had shown refractory on prior lenalidomide and (or) bortezomib therapy. Moreover, elder patients and high‐risk cytogenetic abnormalities were not negative predictors for pomalidomide response after lenalidomide and (or) bortezomib failure. Copyright © 2015 John Wiley & Sons, Ltd.     

Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression

BACKGROUND:

A rapid and early monoclonal (M) protein response during initial therapy in patients with multiple myeloma had been identified as a predictor of superior long‐term outcome in some—but not all—studies.

METHODS:

To determine if the parameter of M protein reduction was of value in the relapsed and/or refractory setting, retrospective landmark analyses were performed at the end of cycles 2 and 4 of a phase 3 study, which randomized such patients to receive bortezomib alone or pegylated liposomal doxorubicin (PLD) with bortezomib.

RESULTS:

Compared with a <25% reduction in M protein at the landmark time point, patients with a 50% to <75% reduction after cycle 2 had a significantly lower hazard ratio (HR) for time to progression (HR = 0.41; 95% confidence interval [CI], 0.26‐0.64; P <.001), as did those with a ≥75% reduction (HR = 0.26; 95% CI, 0.15‐0.45; P < .001). In all of these groups, PLD + bortezomib provided superior outcomes to bortezomib alone, and did so without an increase in the risk of adverse events overall and with a predictable toxicity profile.

CONCLUSIONS:

These analyses supported the possibility that a robust early M protein response is a good prognostic factor for long‐term outcome of myeloma patients with relapsed and/or refractory disease receiving bortezomib or PLD + bortezomib. Cancer 2011;. © 2011 American Cancer Society.     

硼替佐米联合地塞米松治疗多发性骨髓瘤20例临床疗效分析

目的 分析硼替佐米联合地塞米松（PD）化疗方案治疗多发性骨髓瘤（multiple myeloma,MM）患者的疗效和不良反应.方法 回顾性分析20例（初治12例,复发8例）采用PD基础方案化疗（硼替佐米1.0～1.3mg/m2 iv,d1、d4、d8、d11,地塞米松10 ～20 mg iv,d1 ～2,d4～5,d8～9,d11～12,21天为1个疗程,2～3个疗程）患者的临床资料,根据EBMT标准观察疗效,根据NCI-CTCAE标准判断不良反应.结果 PD组12例初治患者6例CR （50％）,5例PR （41.6％）,1例MR（8.4％）,ORR为91.6％;8例复发患者,3例CR （37.5％）,3例PR （37.5％）,1例MR （12.5％）,1例PD （12.5％）,ORR为75％,PD组总的ORR为85％.主要不良反应有胃肠道症状（8例）、Ⅰ～Ⅱ级周围神经炎（6例）、带状疱疹（3例）、血小板减少NCICTCAE 2级（3例）、低血压（1例）.结论 硼替佐米联合地塞米松治疗MM起效快,完全缓解率高,不良反应低.