国产与进口硼替佐米治疗多发性骨髓瘤的真实世界疗效、安全性及经济学对比

目的:在真实世界中,对比以国产与进口原研硼替佐米为基础的方案治疗多发性骨髓瘤的疗效、不良反应及治疗费用。方法:101例多发性骨髓瘤患者,应用进口原研硼替佐米治疗组48例,国产硼替佐米治疗组53例,比较两组患者的治疗反应率、不良反应发生率及治疗费用。结果:随访截止至2018年12月31日,两组患者4个疗程结束后的完全缓解（complete response,CR）率、总缓解率（overall response rate,ORR）差异无统计学意义（P＞0.05）;根据不同危险因素进行分层,两组患者的CR率、ORR差异也无统计学意义（P＞0.05）;在血液学与非血液学不良反应方面差异无统计学意义（P＞0.05）;国产硼替佐米各个疗程后总花费均低于进口硼替佐米,差异具有统计学意义（P＜0.05）。结论:在真实世界中,国产硼替佐米与进口原研硼替佐米治疗多发性骨髓瘤患者在早期诱导缓解方面的临床疗效相当,安全性相当,但国产硼替佐米价格相对低廉,可以广泛应用。     

硼替佐米周疗方法治疗多发性骨髓瘤10例临床分析

目的:探讨硼替佐米周疗方法治疗多发性骨髓瘤的疗效及周围神经病变等相关不良反应。方法:回顾性分析10例多发性骨髓瘤使用硼替佐米周疗病例的疗效。其中初诊6例,复诊4例。全部病例均使用硼替佐米周疗方案:硼替佐米1.3mg/m2第1、8、15及22天静推,沙利度胺75mg第1-35天口服,氟美松15mg第1、2、8、9、15、16、21及22天静推。完成至少2次化疗者可进行评估。结果:10例患者均接受硼替佐米周疗。可评估7例,其中CR 6例,VGPR 1例。无患者出现周围神经病变,不良反应主要为带状疱疹(2/7)。结论:硼替佐米周疗方法治疗初诊多发性骨髓瘤效果良好且不良反应较少,对于治疗复发多发性骨髓瘤的优势有待于进一步评估。     

伐昔洛韦预防多发性骨髓瘤并发带状疱疹的有效性及对患者血清IFN-γ、IL-6水平的影响

目的:探讨伐昔洛韦预防多发性骨髓瘤并发带状疱疹的疗效及对患者血清IFN-γ和IL-6水平的影响。方法:将100例我院收治的多发性骨髓瘤患者随机分为观察组及对照组。两组患者均接受PAD化疗方案,观察组患者在此基础上口服盐酸伐昔洛韦片。比较两组患者治疗后的疗效、带状疱疹发生率及不良反应发生情况;比较两组患者治疗前及治疗后血清IFN-γ、IL-6及T淋巴细胞亚群(CD3＋、CD4＋、CD8＋及CD4＋/CD8＋)水平。结果:两组患者总有效率相比较无统计学差异(P＞0.05);观察组患者带状疱疹发生率(2.0%)低于对照组患者(20.0%)(P＜0.01);观察组患者恶心呕吐及乏力发生率均高于对照组患者(P＜0.05);治疗后,观察组患者血清IFN-γ水平高于对照组患者(P＜0.01),IL-6水平低于对照组患者(P＜0.01);治疗后,观察组患者血液CD3＋、CD4＋及CD4＋/CD8＋水平均高于对照组患者(P＜0.01),CD8＋水平低于对照组患者(P＜0.01)。结论:伐昔洛韦能够有效预防多发性骨髓瘤患者化疗期间带状疱疹的发生,不影响化疗的疗效,同时安全性较高,并能够调节IFN-γ、IL-6及T淋巴细胞亚群的水平。     

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。     

硼替佐米联合毛喉素诱导硼替佐米耐药骨髓瘤细胞凋亡的实验研究

背景与目的：硼替佐米作为蛋白酶体抑制剂已成为新诊断和复发多发性骨髓瘤患者临床治疗的主要药物,但仍有部分患者对硼替佐米产生耐药而影响其长期生存。近年来研究发现,提高细胞内环腺苷酸浓度可以诱导骨髓瘤细胞凋亡并延缓其生长,成为骨髓瘤治疗新途径。该研究通过观察硼替佐米联合腺苷酸环化酶激动剂毛喉素(forskolin)对硼替佐米耐药骨髓瘤细胞的作用,探究克服骨髓瘤耐药的可能途径及其机制。方法：以硼替佐米耐药骨髓瘤细胞株H929-R和原代细胞为模型,通过观察细胞生长、形态、凋亡相关基因的改变来研究硼替佐米、毛喉素单独或联合处理对硼替佐米耐药细胞增殖及凋亡的影响;并应用Rh123/PI双染法检测药物处理前后细胞内线粒体跨膜电位的变化;同时采用实时荧光定量聚合酶链反应(real-time lfuorescent quantitative polymerase chain reaction,RTFQ-PCR)和蛋白[质]印迹法(Western blot)检测线粒体凋亡相关基因转录水平及抗凋亡基因Bcl-2和Mcl-1的蛋白水平的改变。结果：硼替佐米(20 nmol/L)与毛喉素(50 nmol/L)能够协同诱导硼替佐米耐药细胞凋亡。进一步研究发现,毛喉素可协同硼替佐米促使耐药细胞内线粒体跨膜电位下降并下调其Bcl-2和Mcl-1蛋白的表达。结论：毛喉素联合硼替佐米能够诱导硼替佐米耐药骨髓瘤细胞凋亡。     

硼替佐米联合常规化疗治疗多发性骨髓瘤的疗效观察

目的探讨硼替佐米联合常规化疗在多发性骨髓瘤中的治疗效果。方法选取2013年10月至2018年10月间山东省立第三医院收治的80例多发性骨髓瘤患者,根据治疗方式不同分为研究组和对照组,每组40例。对照组患者采用常规化疗(阿霉素+长春新碱+地塞米松),研究组患者在对照组基础上加用硼替佐米,比较两组患者治疗效果、不良反应和心理状态变化。结果研究组患者治疗有效率为95. 0%,高于对照组的85. 0%,差异有统计学意义(P <0. 05)。两组患者不良反应发生率比较,差异无统计学意义(P> 0. 05)。治疗后,研究组心理状态评分低于对照组,差异有统计学意义(P <0. 05)。结论多发性骨髓瘤患者采用硼替佐米联合常规化疗治疗,效果确切,可在临床推广。     

低剂量硼替佐米联合阿霉素及地塞米松治疗多发性骨髓瘤的临床观察

目的：探讨低剂量硼替佐米联合阿霉素及地塞米松治疗多发性骨髓瘤临床效果。方法将45例多发性骨髓瘤患者随机分为观察组23例和对照组22例。对照组采用常规剂量硼替佐米联合阿霉素及地塞米松治疗,观察组采用减低剂量硼替佐米联合阿霉素及地塞米松治疗。观察2组患者的治疗效果,疾病进展时间,不良反应发生情况及患者术后生活质量的改善情况。结果观察组和对照组的治疗有效率分别为52．17％和40．91％,差异无统计学意义（χ2＝0．5733,P＝0．4490）;观察组和对照组的疾病控制率分别为86．96％和81．82％,差异也无统计学意义（χ2＝0．2260,P＝0．6345）。2组患者疾病进展时间为3～10个月,观察组平均进展期（5．78±2．12）个月;对照组平均进展期（5．82±2．08）个月,差异无统计学意义（t＝0．0639,P＝0．9494）。2组患者治疗后主要的胃肠毒性的发生率和带状疱疹的发生率比较,差异有统计学意义（P＜0．05）,而血液毒性各项不良反应发生率大致相当,差异均无统计学意义（P＞0．05）。2组患者治疗后的生活质量评分比较,差异无统计学意义（χ2＝0．8756,P＝0．3494）。结论低剂量硼替佐米联合阿霉素及地塞米松治疗多发性骨髓瘤的疗效与常规剂量相当,且不良反应较小,适合临床长期推广应用。     

硼替佐米诱发周围神经病变发病机制的研究进展

硼替佐米是一种20S蛋白酶体抑制剂，通过干扰细胞信号转导、导致细胞周期阻滞、诱发细胞凋亡、抑制血管生成等机制发挥其抗肿瘤作用，是我国目前治疗多发性骨髓瘤一线用药，但会导致各种不良反应，其中周围神经病变是导致患者停用硼替佐米的原因之一。近年来硼替佐米诱发的周围神经病变的发病机制受到广泛关注，现对其发病机制作一综述。     

多发性骨髓瘤57例疗效分析

 目的　研究以硼替佐米为主的方案和 MPT 方案治疗初治、复发难治多发性骨髓瘤（MM）的疗效及安全性。方法　27例患者接受以硼替佐米为主的 方案化疗（硼替佐米组）,中位治疗3个（1～5个）疗程,30例患者接受 MPT 方案化疗（MPT组）。采用EBMT及WHO标准判断疗效及不良反应。结果　硼替佐米组：1个疗程后总有效 21例 （77.8 %）;治疗结束后总有效24例（88.8 %）,初治组及复发难治组总有效分别为15、9例,总有效率（ORR）分别为 94.0 %、82.0 %。MPT 组：治疗结束后总有效15例（50.0 %）,初治组总有效12例（44.0 %）,复发难治组总有效3例。治疗结束后硼替佐米组对初治及复发难治患者的ORR优于 MPT 组（P＜0.05）。硼替佐米组周围神经病变、带状疱疹及Ⅲ～Ⅳ级血小板减少的发生率分别为37.0 %（10例）、26.0 %（7例）、37.0 %（10例）,高于 MPT 组,但 MPT 组Ⅲ～Ⅳ级贫血的发生率为70.0 %（21例）,高于硼替佐米组。硼替佐米对于肾功能异常及肾功能正常患者疗效相近,各种不良反应无明显增加。MPT组4例肾功能异常患者,3例在5个周期治疗后血清肌酐水平降至正常。结论　以硼替佐米为主化疗方案相对 MPT 方案治疗MM更为有效,初治、复发难治及肾功能异常患者均可受益,且不良反应轻微,患者耐受性好。     

Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy

BACKGROUND:

Humoral‐mediated as well as cell‐mediated immunity is compromised in myeloma patients receiving treatment. Immunocompromised patients are at risk of developing herpes zoster. There is evidence from clinical trials that bortezomib therapy is associated with a significant risk of herpes zoster. It is the authors' clinical policy to administer long‐term acyclovir prophylactically to all symptomatic myeloma patients.

METHODS:

A retrospective review of the records of 125 myeloma patients who were treated with bortezomib and who also received routine acyclovir prophylaxis at the dose of 400 mg daily in >80% of patients was undertaken. Alternatives, used in <20% of patients, were 200 mg of acyclovir, 250/500 mg of valacyclovir, or 500 mg of famciclovir administered daily. This was accompanied by patient education regarding the importance of compliance with these prophylactic medications.

RESULTS:

The duration of bortezomib therapy was 1 to 164 weeks (median, 16 weeks). The total duration of exposure to bortezomib was 4150 weeks (80 patient‐years). Except for the occasional missed dose, the self‐reported compliance with antiviral prophylaxis was 100%. Not a single episode of herpes zoster was reported during this period. No adverse effects were noted that could be definitely attributed to acyclovir, valacyclovir, or famciclovir.

CONCLUSIONS:

Daily acyclovir (or a suitable alternative) appears to be effective at preventing herpes zoster virus in patients with myeloma who are receiving bortezomib, with or without corticosteroids. Cancer 2009. © 2008 American Cancer Society.     

Varicella-Zoster Virus Prophylaxis with Low-Dose Acyclovir in Patients with Multiple Myeloma Treated with Bortezomib

BackgroundVaricella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.Patients and MethodsWe studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m² was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.ResultsA total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.ConclusionVaricellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.     

Decrease in CD4+ T-Cell Counts in Patients With Multiple Myeloma Treated With Bortezomib

BackgroundBortezomib is highly effective in multiple myeloma and is widely used in this disease. Recently, an increased incidence of varicella zoster virus (VZV) reactivation was reported in patients with myeloma undergoing bortezomib treatment.Patients and MethodsWe investigated the influence of bortezomib on T-cell subpopulations in 53 patients with myeloma before initiation of bortezomib and during therapy.ResultsA decrease of CD4+ T cells was seen in 41 of 53 patients (77%). The median CD3+/CD4+ lymphocyte counts declined from 494/μL (range, 130-2187/μL) to 274/μL (range, 41-1404/μL) during bortezomib treatment (P < .001). In the majority of patients (40 of 53 patients, 75%), CD4+ lymphocytes dropped to < 400/μL during bortezomib treatment, and in 18 of 53 patients (33.9%) the CD4+ T cells fell below 200/μL. The minimum CD4+ cell count was observed at a median of 6 weeks (range, 2-22 weeks) after initiation of treatment. The incidence of herpes zoster reactivation was 5.7% in the whole population of patients with myeloma receiving bortezomib. Nineteen of 53 patients received acyclovir at a dose of 400 mg daily as prophylaxis against VZV reactivation. In this group, none of the patients developed herpes zoster. The incidence of VZV reactivation in patients not receiving acyclovir was 3 of 34 (8.8%). Importantly, occurrence of herpes zoster was associated with reduced CD4+ T-cell subpopulation: all patients who developed herpes zoster had CD4+ lymphocytes < 400/μL.ConclusionOur results show that bortezomib leads to a transient decrease in CD4+ lymphocytes, accompanied by an increased incidence of VZV infections. The antiviral prophylaxis with acyclovir is effective in patients with myeloma treated with bortezomib.     

Safety evaluation of bortezomib in multiple myeloma patients with severe renal failure

Recently, the safety and effectiveness of bortezomib for patients with multiple myeloma and renal failure has been reported. In this study, we retrospectively analyzed the 8 myeloma patients with renal failure who have received bortezomib in our hospital.One patient had already required constant hemodialysis before bortezomib.Bortezomib treatment was performed for 229 days, during which time it was injected 30 times.The other 2 patients with chronic renal failure also showed no further renal impairment due to bortezomib.In the remaining 5 patients, serum creatinine levels decreased through 2 cycles(total: 8 injection)of bortezomib treatment.Two patients were complicated with herpes zoster, and 2 patients were complicated with neuropathy in grade 3.We showed the safety and efficacy of bortezomib in Japanese patients with multiple myeloma complicated with renal failure.We should positively consider the therapeutic choice of bortezomib for the refractory myeloma with renal failure.     

硼替佐米和沙利度胺联合VAD方案治疗多发性骨髓瘤疗效分析

目的探讨硼替佐米、沙利度胺联合VAD方案治疗多发性骨髓瘤（MM）的临床疗效。方法 18例初诊MM患者采用硼替佐米、沙利度胺联合VAD方案治疗（A组）,硼替佐米1.3 mg/m2,沙利度胺从100 mg/d开始口服,逐渐增加剂量,至200 mg/d。单纯使用VAD方案（B组）治疗的23例初诊MM患者作为对照组。结果 A组的治疗有效率优于B组（P〈0.05）,联合治疗组的不良反应有皮疹、便秘、神经毒性、乏力、嗜睡、脱发及感染。结论硼替佐米和沙利度胺联合VAD方案治疗MM疗效明显优于VAD方案,缓解率高,对于初诊性MM是疗效较好而又较安全的方案,在选择化疗方案时可优先考虑。     

Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma

BackgroundBortezomib has significantly advanced the treatment of patients with multiple myeloma (MM). However, considering that most patients with MM are elderly, bortezomib-related morbidity should be thoroughly studied to ensure the safe use of this drug. Herpes zoster has been reported as a possible adverse event associated with bortezomib because a major target of bortezomib, nuclear factor—κB, is known to be involved with T-cell immunity.Patients and MethodsWe performed a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing regimen.ResultsDuring the patients' pre-bortezomib treatment (median, 2.14 years), the incidence of herpes zoster was 11% (31 of 282 patients). However, after the patients were treated with bortezomib, the incidence increased to 22.3% (63 of 282 patients), of which almost all occurrences were within the first 3 cycles (median duration, 41 days). The time interval from diagnosis to bortezomib initiation date was shorter in herpes zoster—positive patients than in herpes zoster—negative patients (2.14 ± 1.87 years vs. 3.38 ± 2.95 years; P = .002). Disease duration, previous herpes zoster infection, disease stage and type of myeloma, and the type and intensity of previous treatments failed to show any relationship with herpes zoster. These findings suggest that longer history of disease and treatments did not affect the occurrence of herpes zoster, nor did the type of bortezomib regimens or their toxicities.ConclusionBortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments, and concomitantly administered drugs. Thus, the occurrence of herpes zoster should be monitored during bortezomib treatment.     

The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens

BACKGROUND:

Although treatment for multiple myeloma (MM) has considerably improved in the past decade, MM continues to be an incurable hematological malignancy that causes most patients to eventually relapse and die from their illness. Thus, the identification of effective salvage strategies remains a priority.

METHODS:

In this trial, the authors evaluated the safety and efficacy of bortezomib and dexamethasone [V: on days 1 and 15 (1.3 mg/mq); D: on days 1‐2 and 15‐16, every 28‐day cycle until progression (20 mg/d)] as maintenance therapy (MT) in patients with advanced MM who responded to salvage therapy that used a bortezomib‐containing regimen.

RESULTS:

Forty‐nine MM patients were enrolled in this study between October of 2004 and April of 2008. All patients who were included in this study were responsive to a prior salvage therapy with bortezomib and had a measurable disease. The bortezomib and dexamethasone MT improved the quality of responses to complete remission in 4 patients and very good partial response in 3 patients. In addition, 10 patients experienced at least a 50% improvement in their symptoms. The median time to progression (TTP) was 16 months with a progression‐free survival of 61% after 1 year. The overall response after 1 year was 76%, and the cumulative incidence of death due to disease progression, which was adjusted for competitive risk events, was 14%. Non‐dose‐limiting toxicities included neuropathy (predominantly grade 1), herpes zoster reactivation, pneumonia, and gastrointestinal affections (constipation and diarrhea). Three patients developed grade 2 neuropathy, which required a bortezomib dose reduction to 1.0 mg/mq. No grade 3 or 4 toxicities were recorded.

CONCLUSIONS:

The use of bortezomib and dexamethasone as MT in advanced MM was effective and well tolerated. The twice‐monthly bortezomib infusion appeared to reduce the incidence of grade 3 and 4 neuropathies in comparison to similar experiences in other settings. Cancer 2011. © 2010 American Cancer Society.     

硼替佐米治疗复发难治性多发性骨髓瘤43例

目的 观察硼替佐米联合地塞米松、甲泼尼龙或其他化疗药物治疗复发难治多发性骨髓瘤(MM)的临床疗效与不良反应.方法 43例复发难治MM患者.男34例,女9例,年龄36～72岁,平均年龄58.13岁.其中31例接受硼替佐米联合甲泼尼龙或地塞米松(VMP或VD)方案治疗,12例接受硼替佐米联合环磷酰胺、泼尼松、沙利度胺(VCPT)治疗或联合环磷酰胺、地塞米松、顺铂、依托泊苷(VDECD)治疗,每个患者至少接受2～8个疗程的治疗.采用Biadè标准评价疗效,按照美国国立癌症研究所常规毒性判断标准(NCI CTCAE3.0)判断不良反应.结果中位随访9个月,复发难治患者43例,完全缓解(CR)5例(11.6%),接近CR(nCR)11例(25.6%),部分缓解(PR)15例(34.9%),轻微反应(MR)5例(11.6%).总有效率(CR+nCR+PR+MR)83.7%.主要不良反应有乏力、胃肠道症状、周围神经病变、不同程度的血小板减少、皮疹及带状疱疹等,经过对症治疗以及调整剂量后均能改善.结论 硼替佐米联合其他药物治疗复发难治MM是一种安全可靠、有较好治疗前景的方法 .     

硼替佐米治疗复发难治性多发性骨髓瘤43例

 目的　观察硼替佐米联合地塞米松、甲泼尼龙或其他化疗药物治疗复发难治多发性骨髓瘤（MM）的临床疗效与不良反应。方法　43例复发难治MM患者,男34例,女9例,年龄36～72岁,平均年龄58.13岁,其中31例接受硼替佐米联合甲泼尼龙或地塞米松（VMP或VD）方案治疗,12例接受硼替佐米联合环磷酰胺、泼尼松、沙利度胺（VCPT）治疗或联合环磷酰胺、地塞米松、顺铂、依托泊苷（VDECD）治疗,每个患者至少接受2～8个疗程的治疗。采用Bladè标准评价疗效,按照美国国立癌症研究所常规毒性判断标准（NCI CTCAE3.0）判断不良反应。结果　中位随访9个月,复发难治患者43例,完全缓解（CR） 5例（11.6 %）,接近CR（nCR）11例（25.6 %）,部分缓解（PR）15例（34.9 %）,轻微反应（MR）5例（11.6 %）。总有效率（CR+ nCR+ PR+ MR）83.7 %。主要不良反应有乏力、胃肠道症状、周围神经病变、不同程度的血小板减少、皮疹及带状疱疹等,经过对症治疗以及调整剂量后均能改善。结论　硼替佐米联合其他药物治疗复发难治MM是一种安全可靠、有较好治疗前景的方法。     

Phase I/II study of bortezomib‐melphalan‐prednisolone for previously untreated Japanese patients with multiple myeloma

This phase I/II study was conducted to evaluate the safety and efficacy of bortezomib‐melphalan‐prednisolone in Japanese patients with previously untreated multiple myeloma who are ineligible for hematopoietic stem cell transplantation. One hundred and one patients were enrolled, and 99 patients received up to nine 6‐week cycles of bortezomib (0.7/1.0/1.3 mg/m²) on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1–4 and on days 1, 8, 22, and 29 in cycles 5–9, with melphalan (9 mg/m²) and prednisolone (60 mg/m²) on days 1–4 of each cycle. The recommended dose was determined in the phase I portion, and the overall response rate and safety of bortezomib‐melphalan‐prednisolone at the recommended dose were assessed in the phase II portion. The recommended dose of bortezomib was determined to be 1.3 mg/m². Grade 3 or higher non‐hematological adverse events included diarrhea (12%) and peripheral neuropathy (10%); grade 4 hematological adverse events included lymphopenia (41%), neutropenia (30%), and thrombocytopenia (22%). Eleven patients had lung injury associated with bortezomib; two had grade 3 disease, and the other nine had grade 1 or 2 disease. Of the 86 patients treated with 1.3‐mg/m² bortezomib in phases I and II, the median number of treatment cycles was 4.5, and the overall response rate was 70% (95% confidence interval: 59–79%). Bortezomib‐melphalan‐prednisolone with 1.3‐mg/m² bortezomib was considered to be tolerable and effective in Japanese patients with previously untreated multiple myeloma. However, further investigation is needed to refine the administration schedule.