沙立度胺联合MP化疗方案治疗初治多发性骨髓瘤27例疗效观察

目的:观察沙立度胺联合MP方案,即马法兰加泼尼松治疗多发性骨髓瘤的疗效及其不良反应。方法:确诊的多发性骨髓瘤患者27例。沙立度胺加MP方案:沙立度胺自MP方案开始持续给药,剂量从每天50~200mg开始,每周日剂量递增50mg,至患者不能耐受或最高至每天400mg,MP方案每月1个疗程。结果:初治患者27例部分缓解16例(59.3%),进步6例(22.2%),总有效率为22/27(81.5%)。结论:沙立度胺加MP方案可作为治疗多发性骨髓瘤的治疗选择。不良反应可耐受。     

持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤的临床疗效观察

目的:观察持续小剂量地塞米松加沙立度胺对难治性多发性骨髓瘤的疗效.方法:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤21例,治疗方法用沙立度胺初始剂量100～200 mg/d,晚上1次顿服,从100 mg开始的患者过2周后加量至200 mg,以后维持在200 mg,地塞米松给予1.5 mg,每天2次口服,二药联合小剂量应用,持续3个月,在后1个半月,地塞米松可减量至1.5 mg,每天1次.3个月后进行化疗1个疗程,3个月为1个周期.结果:2个周期治疗后有6例部分缓解,9例进步,6例无效,其中3例加重,总有效率达71.4%.结论:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤疗效确切,不良反应少.     

TAC方案治疗难治复发性多发性骨髓瘤17例

目的：评估沙利度胺、亚砷酸和维生素C（TAC）联合治疗难治复发性多发性骨髓瘤（MM）的有效性和安全性。方法：TAC方案治疗17例难治复发性MM。沙利度胺每晚睡前口服，初始剂量100mg／d，然后每周剂量递增50mg／d，维持剂量100～200mg／d（依病人耐受情况）；亚砷酸10mg／d，静脉滴注，亚砷酸结束后15min维生素C3g／d，静脉滴注，每周5次；用4周休2周为一疗程，连用3～6个疗程。结果：17例患者人组，14例可评估（3例因不良反应明显退出实验组）。完全缓解1例（7．14％），部分缓解3例（21．43％），进步6例（42．86％），无效4例（28．57％），总有效率71．43％，无严重不良反应，常见为乏力、便秘、水肿、皮疹、肝功能轻度异常等。结论：TAC方案治疗难治复发性MM有良好的耐受性和较少的不良作用，治疗顺从性好，有效率高。     

地塞米松联合沙立度胺治疗多发性骨髓瘤临床观察

目的:观察大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤的临床疗效.方法:10例多发性骨髓瘤患者,包括3例髓外浆细胞瘤患者.其中沙立度胺剂量50～200 mg/d口服,同时联合大剂量地塞米松40 mg静脉滴注,连续4 d,间隙5 d,治疗3个月.结果:完全缓解(CR)2例,部分缓解(PR)2例,进步2例,无效4例,其中3例为髓外浆细胞瘤患者;不良反应可耐受,轻度便秘多见.结论:大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤短期内安全有效,而对髓外浆细胞瘤患者效果不佳.     

小剂量沙利度胺联合VAD方案治疗多发性骨髓瘤26例临床观察

目的观察小剂量沙利度胺联合VAD方案化疗治疗多发性骨髓瘤的临床疗效及毒副作用。方法对26例多发性骨髓瘤患者,给予沙利度胺100mg／d联合VAO方案化疗,在化疗疗程结束后继续给予沙利度胺100mg／d维持治疗6个月以上。结果部分缓解15例,进步6例,无效5例,有效率为80．8％,不良反应轻,均可耐受。结论小剂量沙利度胺联合VAD方案化疗治疗多发性骨髓瘤安全有效。     

反应停联合三氧化二砷及维生素C治疗多发性骨髓瘤8例分析

目的观察反应停联合三氧化二砷及维生素C治疗多发性骨髓瘤的疗效及不良反应。方法确诊的多发性骨髓瘤患者8例，使用反应停联合三氧化二砷及维生素C的方案：持续口服小剂量反应停（100mg／d），第1周（d1—5）将As2O3 10mg加入液体静滴，后再以维生素C1000mg加入液体静滴；第2—12周，每周两次As2O3 10mg及维生素C1000mg如前使用。结果部分缓解6例（75％），进步1例（12．5％），总有效率87．5％（7／8）。不良反应有乏力，便秘，恶心、呕吐，肝功能受损，浮肿等。结论反应停联合三氧化二砷及维生素c治疗多发性骨髓瘤疗效明显，患者耐受性可，特另Ⅱ适用于有多种并发症的老年患者。     

不同剂量沙利度胺联合化疗方案治疗老年多发性骨髓瘤的临床疗效对比研究

目的 探讨不同剂量沙利度胺联合化疗方案治疗老年多发性骨髓瘤的临床疗效。方法 选取老年多发性骨髓瘤患者共61例随机分为对照组(n=31)和观察组(n=30)。对照组给予沙利度胺(400mg/d) VAD化疗方案,观察组给予沙利度胺(100mg/d) VAD化疗方案。比较两组临床疗效、临床指标及不良反应。结果 观察组和对照组治疗有效率分别为76.7%和83.9%,两组比较无统计学差异(P＞0.05)。治疗后,两组患者血M蛋白、尿素氮、骨髓浆细胞计数均显著降低,血红蛋白及Kamofsky评分均显著提高,与治疗前比较具有统计学差异(P＜0.05)；两组患者治疗后血M蛋白、血红蛋白、尿素氮、骨髓浆细胞计数及Kamofaky评分比较无统计学差异(P＞0.05)。 观察组便秘、口鼻粘膜干燥、乏力、头晕等不良反应发生率显著低于对照组,组间比较具有统计学差异(P＜0.05)；两组腹胀、恶心、皮疹等发生率比较无统计学差异(P＞0.05)。结论 100mg/d沙利度胺或400mg/d沙利度胺联合VAD方案治疗老年多发性骨髓瘤的临床疗效近似,而100mg/d沙利度胺联合VAD方案治疗多发性骨髓瘤的不良反应更轻。     

沙利度胺联合MP治疗多发性骨髓瘤临床观察

目的:观察沙利度胺联合MP治疗多发性骨髓瘤(MM)的临床疗效。方法:42例MM患者,包括2例髓外浆细胞瘤患者。治疗组19例,沙利度胺起始剂量50mg/d,每周剂量递增50mg/d,直至200mg/d维持治疗;同时联合MP方案化疗(马法兰8mg/m2,d1～4,泼尼松2mg/kg,d1～4),每月1个疗程。对照组23例,马法兰、泼尼松的剂量和用法同治疗组。2组患者在第4个疗程结束后判断疗效。结果:治疗组治疗后较治疗前平均血红蛋白浓度升高32.9%、血清肌酐下降65.9%,骨髓瘤细胞百分比下降59.3%、IgG下降65.9%,生活自理状况改善>2级占73.9%;对照组治疗后较治疗前平均血红蛋白浓度升高20.6%、血清肌酐下降35.2%,骨髓瘤细胞百分比下降42.3%、IgG下降28.3%,生活自理状况改善>2级占45.3%。治疗组总有效率73.69%(14/19),对照组总有效率39.13%(9/23),2组间差异有统计学意义(P<0.05)。治疗组皮疹、便秘、嗜睡和水肿较对照组多,其他不良反应2组差异无统计学意义。结论:沙利度胺联合MP方案治疗MM较单用MP方案疗效更明显,患者耐受性较好,而对髓外浆细胞瘤患者效...     

不同剂量沙利度胺联合化疗方案治疗老年多发性骨髓瘤的临床疗效

目的:探讨不同剂量沙利度胺联合化疗方案治疗老年多发性骨髓瘤的临床疗效。方法:选取老年多发性骨髓瘤患者共61例,随机分为A组(31例)和B组(30例)。A组给予沙利度胺(400 mg/d)+VAD化疗方案,B组给予沙利度胺(100 mg/d)+VAD化疗方案。比较2组临床疗效及不良反应。结果:A组与B组治疗有效率分别为83.9%和76.7%(P0.05)。治疗后2组患者血M蛋白、尿素氮、骨髓浆细胞计数均显著降低,血红蛋白及Kamofsky评分均显著提高(均P0.05);治疗后2组患者血M蛋白、血红蛋白、尿素氮、骨髓浆细胞计数及Kamofaky评分比较无统计学差异(P0.05)。B组便秘、口鼻黏膜干燥、乏力、头晕等不良反应发生率显著低于A组(P0.05或P0.01);2组腹胀、恶心、皮疹等发生率比较无统计学差异(P0.05)。治疗后B组股静脉血流峰速度和平均速度均显著提高(P0.05);治疗6个月后B组的肢端疼痛、感觉障碍、麻木感及不宁腿综合征等临床症状较A组改善明显(P0.05);B组各感觉神经传导速度改善明显优于A组(P0.05)。结论:100 mg/d沙利度胺或400 mg/d沙利度胺联合VAD方案治疗老年多发性骨髓瘤的临床疗效近似,100 mg/d沙利度胺联合VAD方案治疗多发性骨髓瘤的不良反应更轻。     

硼替佐米治疗难治/复发性多发性骨髓瘤的疗效观察

目的:了解硼替佐米对难治/复发性多发性骨髓瘤的疗效及不良反应。方法:采用VATD方案(硼替佐米1.3mg/m2,d1,4,8,11;表阿霉素10mg/d,d1~4;甲泼尼龙240~500mg/d,d1~4,8~11;沙立度胺100~200mg/d,d1~11;或VD方案(硼替佐米1.3mg/m2,d1,4,8,11;甲泼尼龙240~500mg/d,d1~4,8~11)治疗11例难治/复发性多发性骨髓瘤。结果:11例患者中,完全/接近完全缓解(CR)率:9.1%(1/11),部分缓解(PR)率:36.4%(4/11);总有效率(CR加PR)为45.5%(5/11)。不良反应主要有末梢神经炎,胃肠道反应,血小板减少等,均可耐受。结论:硼替佐米对部分已对化疗耐药的难治/复发性多发性骨髓瘤仍然有效,并且效果显著;与化疗无交叉耐药,并能延长患者生存期;为多发性骨髓瘤的治疗提供了一种全新的方法。虽然有一些不良反应但都可耐受。     

Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma

OBJECTIVE: Thalidomide is remarkably active in advanced relapsed and refractory multiple myeloma (MM), so that its use has been recently proposed either in newly diagnosed patients or as maintenance treatment after conventional or high-dose therapy. This latter therapeutic approach has risen the concern of side-effects of long-term therapy with this drug. METHODS: We analysed long-term toxicity of 40 patients (27 M, 13 F, median age = 61.5 yr) who received salvage therapy with thalidomide +/- dexamethasone for longer than 12 months (median 15, range 12-44) at our centre. All the patients had achieved at least a stable disease upon treatment with thalidomide alone (200-400 mg/d, n = 20) or thalidomide (200 mg/d) and dexamethasone (40 mg/d for 4 d every 4 wk) (n = 20). RESULTS AND CONCLUSIONS: Neurotoxicity was the most troublesome and frequent toxic effect that was observed after long-term treatment, the incidence averaging 75%. Among these 30 patients symptoms included paraesthesias, tremor and dizziness. Neurotoxicity was grade 1 in six patients (15%); grade 2 in 13 patients (32.5%), thus determining thalidomide dose reduction to 100 mg/d; and grade 3 in 11 patients (27.5%) who had subsequently to interrupt therapy despite their response. Electromyographic study, performed in patients with grade >/=2 neurotoxicity, revealed a symmetrical, mainly sensory peripheral neuropathy, with minor motor involvement. The severity of neurotoxicity was not related to cumulative or daily thalidomide dose, but only to the duration of the disease prior to thalidomide treatment, although no patients presented neurological symptoms at study entry. These results suggest that long-term thalidomide therapy in MM may be hampered by the remarkable neurotoxicity of the drug, and that a neurological evaluation should be mandatory prior to thalidomide treatment, in order to identify patients at risk of developing a peripheral neuropathy.     

Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy

OBJECTIVES: Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side-effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side-effect. METHODS: Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d. RESULTS AND CONCLUSIONS: Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival.     

A multicenter,open‐label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide‐resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1–5, and thalidomide was given orally at 100 mg once daily in each 21‐day cycle. The overall response rate (ORR) of 41 efficacy‐evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher‐dose regimen. Median progression‐free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment‐related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3–4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose‐limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial. Am. J. Hematol. 89:1037–1042, 2014. © 2014 Wiley Periodicals, Inc.     

Thalidomide in consecutive multiple myeloma patients: single-center analysis on practical aspects, efficacy, side effects and prognostic factors with lower thalidomide doses

Purpose: In this single‐center analysis, we assessed whether lower thalidomide doses are feasible and result in favourable treatment response in multiple myeloma (MM) patients. Results: Between May 2001 and October 2006, 38 consecutive MM patients received thalidomide. Their median age was 62.4 yr, all had stage II/III MM and 31.6% had deletion 13q14 (del13q14). Prior to thalidomide, patients had received a median of two treatment lines. The median thalidomide dose was 100 mg/d (range 50–800) and the median treatment duration was 34 wk. The median cumulative thalidomide dose was 24 g. Sixteen patients received thalidomide as a single agent and 22 in combination (+dexamethasone n = 18; others n = 4). The median time‐to‐treatment failure (TTF) after thalidomide initiation was 30.4 wk. Analysis of prognostic factors showed a significantly prolonged TTF without del13q14 (38.1 vs. 8.9 wk with del13q14; P = 0.006). Our analysis of TTF between thalidomide given alone vs. in combinations showed a better TTF for the combination (23.6 vs. 30.6 wk), albeit not reaching significance (P = 0.20). Other parameters, such as age, stage, and prior SCT showed no difference in TTF. Peripheral polyneuropathy (PNP) frequencies were increased with longer (>28 wk) and increased cumulative thalidomide doses (>40 g), which emphasizes (a) the need to carefully escalate thalidomide from 50 to 200 mg/d, thereby reducing side effects and increasing patient compliance, and (b) that PNP occurs more frequently with longer and higher thalidomide doses. Conclusion: The strategy to lower thalidomide doses seems a feasible and attractive approach in MM patients, this being currently tested in prospective randomized trials.     

Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure

Salvage therapy of patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this further limits the use of conventional chemotherapy. Thalidomide, both alone and in combination with dexamethasone, has been demonstrated to be useful in patients with advanced MM, as responses could be achieved in 30-60% of the cases. From May 2000 to November 2003, 20 consecutive MM patients (15 males, five females, median age 66.5 yr) with stage III relapsed/refractory MM and renal failure, defined as serum creatinine >130 mmol/L, gave their informed consent to be enrolled in a clinical trial aimed at evaluating the efficacy and the toxic effects of thalidomide. Three patients were undergoing chronic haemodialysis during the time of entry in the study. Eight patients have been treated with thalidomide as a single agent, at a starting dose of 100 mg/d, that was to be increased to 400 mg/d in case of good tolerance. Twelve patients have been treated with thalidomide at the maximum dose of 200 mg/d plus dexamethasone 40 mg/d for four consecutive days every 4 wk. A >50% decrease in serum or urine M component was observed in nine patients (45%), seven of whom have been treated with thalidomide + dexamethasone and three with thalidomide alone. Six additional patients achieved a minor response (>25% paraprotein decrease); the total response rate was thus 75%. Median response duration was 7 months (range 2-24 months). Four patients were refractory to treatment. Recovery of a normal renal function was observed in 12 of 15 responsive patients, two additional patients, in chronic haemodialysis, showed a reduction of serum creatinine. Toxicity profile of thalidomide with or without dexamethasone was comparable with that observed in patients with a normal renal function. In conclusion, our data show that thalidomide can be safely administered in patients with advanced MM and renal failure.     

Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment

BACKGROUND: Thalidomide is an immunomodulatory drug used in the treatment of relapsed or refractory multiple myeloma (MM). The optimal dosing regimen of thalidomide is not known. PATIENTS AND METHODS: We retrospectively analysed the overall response rate and response duration of 53 patients with relapsed MM who received thalidomide in a median dose of 100 mg daily. The aim of the study was to compare the response rates of thalidomide given as the second-line treatment to those of thalidomide given as the third-line therapy. RESULTS: Of 33 patients receiving thalidomide as second line, 13 (39%) had overall treatment response. Of 20 patients treated with thalidomide monotherapy as the third-line treatment, there were three treatment responses (15%) (P = 0.039). The median duration of treatment response in the second-line thalidomide group (12 months, range 6-60 months) was twice as long as that in the third-line thalidomide group (6 months, range 3-57 months), although the difference was not statistically significant, probably due to low number of patients. Only 6% of patients (3/53) had to stop the treatment because of toxicity. CONCLUSIONS: Monotherapy with low-dose thalidomide results in treatment responses in approximately 30% of patients with advanced MM. The response rate appears to be higher if thalidomide treatment is started after the first relapse or progression in comparison with the second relapse or progression. Treatment toxicity is acceptable even with prolonged exposure to the drug.     

DVd(T)方案治疗多发性骨髓瘤17例临床疗效分析

目的:观察脂质体阿霉素(PLD)联合长春新碱(VCR)、地塞米松(Dex)士沙利度胺(Thal)治疗多发性骨髓瘤(MM)患者的疗效及毒副反应.方法:17例初治或复发难治MM患者接受DVd(PLD 40 mg·m-2d1、VCR 2 mg d1、Dex 40 mg d1～4)或DVdT(PLD及VCR用法用量同上,Dex:40 mg,d1～4、d9～12;Thal:100 mg,d1～21)治疗,按照EBMT标准评价疗效、WHO标准判断毒副反应.结果:①17例患者共完成了34个周期的治疗,总有效率(ORR=CR+nCR+VGPR+PR)为58.8%,与国外文献报道接近,与历史上我院采用的VAD及其类似方案相比疗效也接近.②采用DVd方案治疗的11例患者的ORR为4/11(36.4%).其中6例初治患者的ORR为2/6(33.3%).采用DVdT方案化疗的6例患者均为初治病例,其ORR为6/6(100%).对于初治患者.DVdT方案的ORR显著好于DVd方案.③多数治疗相关毒副反应为1～2级且可耐受.17例患者中有13例在接受DVd(T)化疗前心电图或心脏B超示不同程度的心律失常或左室舒张功能降低,但均未因化疗增加心脏毒性.DVd组与DVdT组的毒副反应接近.结论:DVd方案具有较好的耐受性,适当延长Dex用量并加入Thal可以在不增加化疗相关毒性的同时显著提高DVd方案疗效.     

Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia

Thalidomide is a putative anti-angiogenesis agent that has significant anti-tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed- or refractory-AML previously treated with cytarabine-containing regimens. A total of 16 patients with refractory- or relapsed-AML were treated with thalidomide 200-800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3-94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed- or refractory-AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy.     

Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myélome (IFM) and the Société Française de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC)

Thalidomide is effective in multiple myeloma (MM), even in patients who have relapsed after high-dose therapy. A potent graft-versus-myeloma (GVM) effect can be induced against MM after allogeneic stem cell transplantation (allo-SCT). In all, 31 MM patients received thalidomide as a salvage therapy after progression following allo-SCT. The median maximum daily dose of thalidomide was 200 mg (range, 50-600). Thalidomide had to be discontinued in six patients (19%) because of toxicity. In all, nine patients (29%; 95% CI, 13-45) achieved an objective response with thalidomide therapy (six partial and three very good partial responses, VGPR). Five patients developed graft-versus-host disease (GVHD) after thalidomide therapy, including the three patients achieving a VGPR. These data demonstrate that thalidomide is potentially effective in MM patients failing allo-SCT.     

Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma

Thalidomide, the prototype of a new class of agents active against multiple myeloma (MM), exerts synergistic/additive effects when combined with other drugs. The aim of this study was to compare the toxicity and efficacy of thalidomide alone and in combination with oral melphalan. Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day (n=23; T group), alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days (n=27; TM group). A>/=50% paraprotein reduction was observed in 59% of TM compared with 26% of T patients (P=0.009); three TM patients were found to have an absence of paraprotein by immunofixation. After a median follow-up of 13 months (range 6-32), progression-free survival (PFS) at 2 years was significantly longer in the TM group (61 versus 45%; P=0.0376), whereas overall survival did not differ significantly. Toxicity was not significantly greater with the combination therapy; although DVT was more frequent (11 versus 4%), as was grade 3 leukopenia (30 versus 13%; P=0.073), there were no cases of severe infection. Thalidomide administered with oral melphalan improved response rates and PFS in patients with advanced MM without significantly increasing severe toxicity.