硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤近期疗效分析

目的:分析硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤(MM)患者的临床疗效和不良反应.方法:初治MM患者11例,复发、难治MM患者7例均采用VD方案化疗:硼替佐米1.0～1.3 mg/m2第1、4、8和11天快速静脉注射,地塞米松20 mg第1～4天(7例复发难治予地塞米松40 mg)静脉滴注,3周为1疗程,所...     

硼替佐米联合环磷酰胺和地塞米松治疗多发性骨髓瘤28例临床观察

目的:观察硼替佐米联合环磷酰胺和地塞米松治疗多发性骨髓瘤的临床疗效和药物不良反应。方法:对28例初发和复发难治性多发性骨髓瘤用硼替佐米1.0～1.3mg/m2,每疗程的第1、4、8、11天静脉注射;环磷酰胺0.3g/m2,每疗程的第1、4、8、11天静脉注射;地塞米松40mg/d,每疗程的第1～2天、第4～5天、第8～9天及第11～12天静脉滴注,每28d为1个疗程,接受4个疗程的治疗,同时在每个疗程的开始进行骨髓细胞学、血M蛋白、β2-微球蛋白(β2-MG)进行检测,并观察药物的不良反应。结果:①28例患者都有效,有效率为100%,其中完全缓解(CR)8例,CR率为28%,接近完全缓解(nCR)2例,部分缓解(PR)13例,轻微反应(MR)5例。②骨髓瘤细胞百分比、M蛋白含量、β2-MG含量在化疗前后均差异有统计学意义(均P<0.05)。③不良反应以胃肠道反应最为常见,同时也可出现血小板减少,带状疱疹,周围神经病变等。结论:硼替佐米联合环磷酰胺和地塞米松对初发和复发难治性多发性骨髓瘤有明显的临床疗效,且药物不良反应较轻,耐受性良好。     

硼替佐米联合VAD方案治疗多发性骨髓瘤

目的：观察硼替佐米联合VAD方案治疗初治、难治复发多发性骨髓瘤（MM）患者的疗效及安全性。方法：15例初治及难治复发MM患者,硼替佐米1.3mg/m2,d1、4、8、11或d0、3、7、10静脉注射,每28d1个疗程;每个疗程联合VAD方案化疗,每位患者接受2-6个疗程治疗。采用2006年MM国际统一疗效标准观察疗效,并按NCI/PNIH标准判断不良反应。结果：中位随访14个月,治疗总有效率80%,其中8例患者达完全缓解,1例患者达良好的部分缓解,3例患者达部分缓解,2例患者疾病无进展,1例患者治疗过程中疾病进展。最常见的不良反应包括胃肠道症状,不同程度的白细胞、血小板减少,周围神经病和乏力等,经对症治疗及调整用药剂量后均能改善。结论：硼替佐米联合VAD方案可提高MM患者治疗完全缓解率,并未增加周围神经毒性。     

硼替佐米为主的联合方案治疗初治多发性骨髓瘤

目的 回顾性比较分析硼替佐米为主方案(VD/VT)与长春新碱联合阿霉素和地塞米松(VAD)方案治疗初治多发性骨髓瘤(MM)的疗效及不良反应.方法 18例初治MM患者采用硼替佐米1.0 mg/m2或1.3 mg/m2,1、4、8、11 d给药;12例联合地塞米松20～40mg,1～4 d;6例联合沙立度胺100mg/d,21d为一疗程.24例MM患者采用VAD方案.结果 硼替佐米组总反应率88.9%(16/18),完全缓解或接近完全缓解率38.9%(7/18),显著优于VAD组,分别为41.7%,4.2%.硼替佐米组主要的不良反应依次为血液系统毒性,胃肠道反应和周围神经病变.VAD组主要不良反应为感染、脱发及静脉炎.结论 硼替佐米为主的联合化疗在初治MM中疗效显著优于VAD组,尤其在高危人群如严重骨质破坏、肾功能不全及不良染色体表现的患者,缓解率高,毒副作用轻,应优先考虑使用.     

硼替佐米及沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤疗效观察

目的:观察硼替佐米、沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤(MM)的临床疗效和不良反应。方法:9例难治复发性MM患者均采用硼替佐米、沙利度胺联合VAD方案治疗。其中,长春新碱0.4mg/d,d1～4;阿霉素10mg/d,d1～4;地塞米松40mg/次,d1～4,d9～12,d17～20;硼替佐米2mg/d,d1,4,8,11;沙利度胺,起始量100mg/d,根据患者情况,逐渐加量至200mg/d,每晚顿服,治疗2个周期。观察疗效,并按WHO不良反应分级标准判断不良反应。结果:9例患者,3例完全缓解/接近完全缓解(CR/nCR),4例部分缓解(PR),1例进步,1例无效,CR加PR率达77.8%,总有效率88.9%。不良反应主要有乏力、便秘、皮疹、胃肠道反应及末梢神经炎,均可耐受。结论:硼替佐米、沙利度胺联合VAD方案治疗难治复发性MM近期疗效显著,耐受性好,是一种新的治疗选择。     

硼替佐米联合地塞米松治疗多发性骨髓瘤临床研究

目的观察硼替佐米联合地塞米松(PD)在多发性骨髓瘤(MM)中的应用。方法 2008年2月至2010年4月北京积水潭医院36例MM患者接受PD治疗。以同期46例VADT化疗的MM患者做为对照。分析病情转归及不良反应。结果 (1)PD用于初治和复发和(或)难治MM患者疗效均显著。初治组治疗有效率85.7%(18/21);复发和(或)难治组的有效率为80.0%(12/15);总有效率为83.3%(30/36)。PD与VADT治疗初治MM的有效率差异无统计学意义(85.7%对78.1%,P=0.740),PD治疗复发和(或)难治MM的有效率明显高于VADT组(80.0%对42.9%,P=0.039)。PD起效快,治疗有效的患者均在1个疗程后达PR;63.9%患者在3个疗程内达到VGPR以上缓解,优于VADT组的30.4%。(2)PD不良反应主要有乏力、周围神经病变及血小板减少等。PD治疗初治MM较复发和(或)难治MM不良反应小,耐受性好,更能坚持长期化疗以获得最大缓解。(3)PD治疗的MM患者骨痛缓解快,全身骨密度增高较VADT组更显著[(1.138±0.102)g/cm2对(1.053±0.137)g/cm2,P=0.039)]。结论硼替佐米联合地塞米松治疗MM缓解率高,可首选用于治疗初治及复发和(或)难治MM。     

硼替佐米和沙利度胺为主的化疗方案对伴有肾功能不全的多发性骨髓瘤患者的疗效比较

目的:观察以硼替佐米为主和沙利度胺为主的化疗方案治疗伴有肾功能不全的多发性骨髓瘤(MM)患者的疗效,探讨对伴有肾功能不全的MM治疗的最佳方案.方法:40例伴有肾功能不全的MM患者,其中初治20例,复发(难治)20例.选择20例使用以硼替佐米为主的化疗方案作为试验组,以同期20例接受沙利度胺为基础的联合化疗方案治疗的MM...     

多发性骨髓瘤VD方案诱导后两种巩固治疗方法的疗效分析

蛋白酶体抑制剂硼替佐米给多发性骨髓瘤(MM)的治疗带来了革命性进步,使初治MM的完全缓解/接近完全缓解(CR/nCR)率达到25%~[1],与自体造血干细胞移植(ASCT)的疗效相似.本研究回顾性分析了经诱导治疗达nCR以上疗效的患者,应用ASCT或含硼替佐米方案两种不同巩固方法的疗效和预后.     

硼替佐米联合地塞米松治疗多发性骨髓瘤疗效及影响因素分析

目的 观察硼替佐米联合地塞米松治疗多发性骨髓瘤患者的疗效、与疗效有关的预后因素及化疗毒副反应.方法 2006年5月至2008年7月中山大学附属第一医院40例初治、难治和(或)复发MM患者接受硼替佐米联合地塞米松(VD)方案治疗,每3周为1个疗程.结果 总反应率75.0%(30/40),完全缓解(CR)+接近完全缓解(nCR)率42.5%(17/40),80.0%(24/30)患者在1个疗程后即可看到疗效,中位达最佳疗效时间为2个疗程.与非轻链患者相比,轻链型患者总反应率(100.0%对65.5%,P=0.038)和CR率(36.4%对6.9%,P=0.039)均明显高于前者,而且起效更快,81.8%(9/11)的患者在1个疗程后即达最佳疗效.VD方案Ⅲ～Ⅳ级不良反应发生率低,包括白细胞减少、血小板减少、腹泻和乏力,经对症治疗或推迟化疗后均可恢复.感染发生率高(35.0%),是重要的死亡原因之一.结论 硼替佐米联合地塞米松治疗MM患者有明显疗效,在轻链型患者疗效更加显著,起效更快,副反应可以耐受.     

硼替佐米联合地塞米松治疗多发性骨髓瘤的临床研究

目的观察硼替佐米联合地塞米松治疗多发性骨髓瘤(MM)的疗效和不良反应。方法2005年6月至2007年7月收集温州医学院附属第一医院14例MM患者,其中男11例,女3例;年龄52~77岁,平均年龄为65.1岁。第1,4,8和11天给予静脉推注硼替佐米1.3mg/m2;第1~4天,8~11天给予地塞米松20~40mg静脉滴注,每例患者接受1~8个疗程的治疗。采用欧洲骨髓移植协作组(EBMT)标准观察疗效,并按美国国立癌症研究所(NCI)(第3版)CTCAE标准判断不良反应。结果中位随访时间为3.5(1.3~10)个月,12例(86%)患者对治疗有效,其中2例完全缓解,6例患者接近完全缓解,3例部分缓解,1例轻微反应;2例进展。14例患者中10例出现不同程度的乏力,7例出现周围神经病变,腓肠肌酸痛2例,4例出现胃肠道症状,5例血小板减少,1例播散型带状疱疹,1例顽固性低钠血症。均经对症治疗基本缓解。结论硼替佐米联合地塞米松是治疗MM的新的有效治疗方法,不良反应稍多,但经对症治疗及调整用药剂量后均能改善。     

A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma

We compared the clinical responses and toxicities between bortezomib-based salvage chemotherapy combined with cyclophosphamide, thalidomide, and dexamethasone(Vel-CTD) and without thalidomide (Vel-CD) in patients with relapsed or refractory MM. Eighty-six patients received at least two cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m2 orally on days 1–4; thalidomide 50–100 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on days 1, 4, 8, and 11 every 3 weeks), and 67 patients were given at least two cycles of Vel-CD, which is the same regimen as Vel-CTD except without thalidomide. The overall response rates of the Vel-CD and Vel-CTD groups were 88% and 90% (p>0.05), respectively. There was no difference in the progression free survival (p = 0.69) and overall survival rates(p = 0.49) between the two groups. Grade 3 or more adverse hematologic events occurred in the same proportion of patients in both groups. In terms of non-hematologic toxicities, the Vel-CTD group showed a higher proportion of autonomic neuropathy, motor neuropathy, and sensory neuropathy compared to the Vel-CD group (each, p<0.05). Only three patients in the Vel-CTD group showed thrombotic events despite aspirin prophylaxis. The Vel-CD regimen inpatients with relapsed or refractory MM is an effective and more tolerable salvage therapy compared to Vel-CTD in terms of its comparable response rate and less severe of non-hematologic toxicities.     

硼替佐米为主的联合方案治疗复发或难治性多发性骨髓瘤

目的 观察硼替佐米为主的联合方案治疗复发、难治性多发性骨髓瘤(MM)的疗效和不良反应,探讨应用硼替佐米治疗的最佳方案、剂量及疗程.方法 复发、难治性MM患者46例,均在3～4周的疗程内,给予硼替佐米1.3 mg/m2,1、4、8、11 d,同时联合地塞米松(D)、D+沙立度胺(T)、环磷酰胺(C)+D、米托蒽醌(M)+D、DC+鬼臼乙叉甙(E)+顺铂(P)和DT-P+阿霉素(A)+CE等化疗方案.采用国际骨髓瘤工作组(IMWG)标准判断疗效,并按美国国立癌症研究院不良事件通用命名标准(NCI CTCAE)(第3版)观察不良反应.以接受沙立度胺为基础的联合方案治疗的49例复发、难治MM作历史对照研究.结果 在可评估的43例患者,中位随访时间10个月,31例获得不同程度的缓解,总有效率为72.1%(对照组为51.0%,P＜0.05).其中完全缓解(CR)5例(11.6%),很好的部分缓解(VGPR)12例(27.9%),部分缓解(PR)14例(32.6%).接受1个疗程和2个疗程的总有效率分别为30.2%、58.1%(P＜0.05).常见的不良反应为血小板减少(62.8%)、乏力(55.8%)、恶心(51.2%)及周围神经病变(30.2%)等,但均能耐受.对照组的不良反应有便秘(69.4%)、乏力(59.2%)和头昏、头晕(46.9%)等.结论 硼替佐米为主的联合方案是一种对复发、难治性MM新的治疗选择,疗效优于沙立度胺为基础的联合方案,且两者毒性谱有所不同.     

Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma

In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.     

A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma

We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with > 1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated dose-escalation schedule in patients with relapsed or refractory MM. The secondary objective was to determine overall response (OR), time to progression (TTP), and overall survival (OS). The MTD identified was bortezomib 1.3 mg/m(2) (days 1, 4, 8, and 11), dexamethasone 20 mg (days 1, 2, 4, 5, 8, 9, 11, and 12), and romidepsin 10 mg/m(2) (days 1, 8, and 15) every 28 days. Thrombocytopenia (64%) was the most common ≥ grade 3 hematologic toxicity. Peripheral neuropathy occurred in 76% of patients (n = 19) (≥ grade 3, 8%; 95% confidence interval [CI] 1%-26%). Maintenance romidepsin 10 mg/m(2) (on days 1 and 8 of a 28-day cycle) proved feasible, with 12 patients receiving a median of 7.5 cycles (range: 1-29). An OR (M-protein) of > minor response (MR) was seen in 18 of 25 patients (72%); 2 (8%) had complete remissions (CRs) and 13 (52%) had partial responses (PRs), including 7 (28%) with very good PRs (VGPRs). The median TTP was 7.2 (95% CI: 5.5-19.6) months, and the median OS was > 36 months. This regimen shows activity with manageable toxicity and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as NCT00431990.     

Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma

A phase 2 trial was performed to study the combination of bortezomib (VELCADE) with intermediate-dose dexamethasone (DEX), and continuous low-dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty-four patients with advanced MM were enroled to receive eight 3-week treatment cycles with bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, followed by three 5-week cycles with bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event-free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.     

PAD方案治疗初治多发性骨髓瘤的疗效研究

目的:观察硼替佐米联合脂质体多柔比星及地塞米松(PAD)方案治疗初治多发性骨髓瘤(MM)的疗效和不良反应。方法:初治MM患者19例,其中男11例,女8例,中位年龄66(43～77)岁。均给予PAD方案为一线治疗:硼替佐米1.3mg/m2,静脉注射,第1、4、8、11天;脂质体多柔比星20mg,静脉滴注,第1、4、8天;地塞米松20mg/d,静脉滴注,第1、4、8、11天,每4周为一个周期。采用国际骨髓瘤工作组(IMWG)标准观察疗效,并按国际肿瘤组织毒副作用统一命名法的标准(NCICTCAE)(第3版)判断不良反应。结果:平均(3.9±1.1)(2～6)个疗程后的疗效观察,总有效率为89%,其中完全缓解(CR)8例(42%),非常好的部分缓解(VGPR)2例(11%),部分缓解(PR)6例(31%),轻微反应(MR)1例(5%),疾病稳定(SD)2例(11%)。可见初始疗效的中位时间为2.8(1～5)周,最佳疗效的中位时间为2.7(1～4)个月。骨髓瘤细胞、血清单克隆蛋白量、红细胞沉降率均较治疗前下降。中位随访期19(6～35)个月,所有患者目前均生存。最常见的不良反应为胃肠道症状,其中便秘7例(37%),腹泻1例(5%),恶心2例(11%),黏膜炎1例(5%)。其次为血液学改变,中性粒细胞减少6例(32%),贫血3例(16%),血小板减少5例(26%)。另外,周围神经病变(PN)较为多见,1～2级4例(21%),3级1例(5%)。3例(16%)患者出现手足综合征,3例(16%)患者出现乏力。结论:PAD方案治疗初治MM疗效明确,不良反应较少。     

A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.     

Therapy with Bortezomib plus Dexamethasone Induces Osteoblast Activation in Responsive Patients with Multiple Myeloma

Bortezomib is a novel proteasome inhibitor that has shown marked antitumor effects in patients with multiple myeloma (MM). We evaluated the feasibility and efficacy of bortezomib plus dexamethasone (BD) therapy and assessed bone metabolism in relapsed or refractory MM. Fourteen patients received 1.3 mg/m2 bortezomib on days 1, 4, 8, and 11 along with 20 mg/dose of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 in a 21-day cycle. After 1 to 3 cycles of BD therapy, 9 patients (64%) achieved an objective response (5 very good partial responses and 4 partial responses). Notably, a rapid increase in the serum concentration of alkaline phosphatase (ALP) was observed in 6 of the treatment-responsive patients. Moreover, serum levels of bone-formation markers (bone-specific ALP and osteocalcin) significantly increased in 5 and 2 responsive patients, respectively. Radiographic examination showed improvement in bone lesions, suggesting that BD therapy induces osteoblast activation in responders. Adverse events included thrombocytopenia of grades 1 to 3, peripheral neuropathy of grades 1 to 2, and grade 3 ileus and were transient and manageable. Although severe lung injury has been reported among Japanese patients treated with bortezomib, no pulmonary complications were observed during BD therapy. Our results suggest that BD therapy is a safe and promising therapeutic approach for Japanese patients with MM.     

Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma

This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m² on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m²) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m² and bortezomib 1·3 mg/m². The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD ( n  = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD ( P  < 0·05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.