Therapeutic application of thalidomide in multiple myeloma.

Treatment with thalidomide and dexamethasone was given to 26 patients with active, previously untreated multiple myeloma (MM). Thalidomide was administered in an initial dosage of 200 mg/d for 2 weeks and then increased as tolerated (in 200-mg increments at 2-week intervals) to a maximum daily dose of 800 mg. Dexamethasone was given orally in a dosage of 40 mg/d on days 1 through 4, 9 through 12, and 17 through 20 in odd cycles and 40 mg/d on days 1 through 4 in even cycles at monthly intervals. Response was defined as a decrease in serum and urine monoclonal (M)-protein by 50% or greater. Twenty (77%) of 26 patients with active MM exhibited a therapeutic response. Among the first seven patients treated with a thalidomide dose of 400 mg, grade III to IV skin toxicity developed in two. Drug titration was then stopped and the thalidomide dose maintained at 200 mg/d. Six (86%) of seven patients showed a response after thalidomide dose escalation, whereas 14 (74%) of 19 patients demonstrated a response with a constant thalidomide dose of 200 mg/d. Thalidomide alone produced a response in six (38%) of 16 patients with smoldering or indolent myeloma. The angiogenesis grade was elevated in only 8% of these patients. Thirty-two patients with relapsed myeloma were treated with thalidomide dosed at 200 mg/d, with 200-mg escalations every 2 weeks to a maximum daily dose of 800 mg. Prior chemotherapy had failed and five (16%) patients had experienced relapse following stem cell transplantation. Ten (38%) of the 26 patients who had received at least two cycles of therapy obtained a response.     

Thalidomide in low doses is effective for the treatment of resistant or relapsed multiple myeloma and for plasma cell leukaemia

Thalidomide is an effective treatment for relapsed multiple myeloma (MM), but is associated with a significant side effect profile at higher doses. In a recent study, only half of the enrolled patients were able to tolerate the maximum dose of 800 mg/day [Singhal, S., et al. (1999) "Antitumor activity of thalidomide in refractory multiple myeloma", New Engl. J. Med. 341, 1565-1571]. Moreover, the dose-response relationship has not been defined. We report our use of low dose thalidomide in a small cohort of 12 patients-eight with relapsed or refractory MM and four with plasma cell leukaemia (PCL). Five of the 12 (42%) patients had a partial response, showing a median fall in their PP/BJP of 80% (63-90%) at a median dose of 175 mg (100-300 mg) with negligible side effects. Three of four patients with PCL showed an impressive response to treatment with thalidomide as a single agent. No patient who failed to show any evidence of response at low dose (<150 mg/day) responded to higher doses. In this study, thalidomide induces a similar rate of response at a lower and better tolerated dose than previously reported and produced "best ever" responses in patients with resistant PCL.     

亚砷酸联合沙利度胺治疗难治性复发性多发性骨髓瘤的疗效

 【摘要】　目的　观察亚砷酸（ATO）联合沙利度胺治疗难治性复发性多发性骨髓瘤（MM）的疗效和安全性。方法　35例难治性复发性MM患者,给予ATO（10 mg／d）及维生素C（2 g／d）静脉滴注,连续应用14 d,每28 d为1个疗程;同时给予沙利度胺口服,起始剂量为50 mg／d,1周后逐步加量并调整至100～150 mg／d,长期维持。连续应用3个疗程后评估疗效和患者不良反应,有效患者继续沙利度胺维持治疗,并随访观察无进展生存（PFS）。采用参照欧洲血液和骨髓移植小组骨髓瘤疗效判定标准判定疗效,并按世界卫生组织（WHO）标准判定不良反应。结果　ATO联合沙利度胺治疗难治性复发性MM总有效率71.43 %（25／35）,完全缓解2例（5.71 %）,部分缓解12例（34.29 %）,微小反应 11例（31.43 %）,无效10例（28.57 %）。25例患者进入维持治疗后,中位随访期为11个月（2～31个月）,中位PFS 9个月。主要不良反应有消化道反应、白细胞减少、肝功能损害、手足麻木等,不良反应轻微,均可耐受。结论　ATO联合沙利度胺治疗难治性复发性MM有效、可行,并有较好的治疗顺从性。     

沙利度胺联合地塞米松治疗难治复发性多发性骨髓瘤的临床研究

 目的 探讨沙利度胺联合地塞米松（Thal-Dex）方案治疗难治复发性多发性骨髓瘤（MM）的疗效及相关毒副作用。方法 采用Thal-Dex方案对15例难治复发性MM患者进行治疗，沙利度胺起始剂量为100 mg，维持两周后逐渐增至200 mg；地塞米松片40 mg口服，第1～4天、第9～12天、第17～20天，4周为1疗程；口服小剂量华法林（1.25 mg／d）预防深静脉血栓（DVT），监测骨髓细胞学浆细胞数、血M蛋白、血β2-微球蛋白及其他常规检查项目。结果 15例患者中完全缓解5例，部分缓解4例，微小反应4例，无反应1例，死亡1例，总体反应率为60.0 %；3例患者发生DVT；全部患者未发生Ⅱ级以上血液毒性。结论 Thal-Dex 方案对于难治复发性MM有较好的疗效，耐受性好，但需注意DVT发生。     

Thalidomide for patients with recurrent lymphoma

BACKGROUND: Thalidomide has significant clinical activity in patients with multiple myeloma. However, its activity against other lymphoid tumors is unknown. The authors reported their experience with thalidomide in patients with recurrent/refractory non-Hodgkin lymphoma and in patients with Hodgkin disease. METHODS: Nineteen patients (median age, 62 years) who had undergone a median of 5 previous treatment regimens were treated with escalating doses of thalidomide (200-800 mg per day) until disease progression or prohibitive toxicity was observed. The authors measured serum levels of angiogenesis factors before and after treatment. RESULTS: One patient (5%) with evidence of recurrent gastric mucosa-associated lymphoid tissue lymphoma achieved a complete response, and 3 patients (16%) achieved stable disease. CONCLUSIONS: The current study suggests that thalidomide has limited single-agent activity in heavily pretreated patients with recurrent or refractory lymphoma.     

Thalidomide in the management of multiple myeloma.

A phase II trial of thalidomide in refractory multiple myeloma was initiated using a dose schedule that escalated from 200 mg/d to 800 mg/d. More than two thirds of patients had cytogenetic abnormalities and more than half had received at least two cycles of high-dose therapy. A paraprotein reduction of at least 25% was noted in 37% of patients and 14% had either a complete remission (CR) or a near CR. No treatment-related mortality was observed. With a median follow-up of almost 2 years, the 2-year event-free survival (EFS) and overall survival (OS) estimates were 15% and 60%, respectively. A reduction of paraprotein levels by greater than 50% was associated with a significant reduction in bone marrow plasmacytosis and beta(2)-microglobulin levels (beta2M), and greater recovery of hemoglobin and IgM levels compared to patients whose paraprotein was reduced by a lesser degree. Responses occurred more frequently among patients with a lower plasma cell labeling index (PCLI) and normal cytogenetics. Comparing response and survival by thalidomide dose for low- and high-risk groups revealed a thalidomide dose-response effect in the high-risk group of patients. The virtual absence of myelosuppressive toxicity, except in heavily pretreated patients with compromised bone marrow function, suggests that thalidomide is an ideal agent to be used in combination with cytotoxic agents and dexamethasone. Several trials are currently underway at the Arkansas Myeloma and Transplantation Research Center to determine the clinical benefit of adding thalidomide to post-transplant salvage therapy and in the upfront management of patients.     

Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program

BACKGROUND: Despite recent advances in systemic and supportive therapies, multiple myeloma remains an incurable plasma cell malignancy. Novel therapeutic approaches are thus needed. Thalidomide has recently been recognized as an effective new agent for previously untreated, refractory or relapsed myeloma. PATIENTS AND METHODS: To evaluate the efficacy and tolerability of thalidomide in myeloma, we performed a retrospective analysis of 21 consecutive patients receiving thalidomide alone or in combination with dexamethasone and/or intermittent cyclophosphamide as first-line, maintenance or salvage therapy within a compassionate use program. RESULTS: Of the 21 patients, 16 (76.2%) had refractory or relapsed disease, including 7 (33.3%) patients relapsing after autologous stem cell transplantation. Three patients received thalidomide as maintenance therapy after having achieved a partial remission following autologous stem cell transplantation or conventional chemotherapy. Two patients were given thalidomide as first-line treatment for indolent disease. During long-term treatment (median 12 months, range 1-27 months), patients tolerated only low doses of thalidomide (50-150 mg/day) due to cumulative neurotoxicity. At a median follow-up of 16 months (range 1.5-28 months), we observed an overall response rate of 61.9% (50% for the subgroup receiving thalidomide alone; 77.8% for combination therapy) consisting of 1 complete response, 2 near-complete responses, 8 partial responses and 2 minor responses. Median progression-free survival was 20 months. CONCLUSIONS: We conclude that low-dose thalidomide (50-100 mg/day) alone or in combination is a safe, well-tolerated and effective form of therapy for patients with myeloma at various stages of disease.     

Low dose thalidomide in patients with relapsed or refractory multiple myeloma

Remarkable results of the treatment of refractory multiple myeloma with thalidomide have been reported. In most preceding studies, the given thalidomide dose was escalated to a maximum tolerated dose of up to 800 mg/d. The frequency of adverse effects correlates with dose intensity. Since a significant gain of therapeutic effects could not be observed as thalidomide dosage was escalated, the optimal dose of thalidomide remains to be determined. We report the results of a study with low dose thalidomide (median administered dose 100 mg/d, range 50-400 mg/d). Twenty-four relapsed (n=19) or resistant (n=5) multiple myeloma patients were included in the study. Twelve patients (50%) received thalidomide as monotherapy, 8 patients (33%) received a combination of thalidomide and dexamethasone (every 4 weeks 40 mg/day for 4 days) and 4 patients (17%) who were resistant to vincristine, doxorubicin, dexamethasone (VAD) received VAD combined with thalidomide. Overall, a response was observed in 12 patients (50%). Of the 12 patients treated with low dose thalidomide alone 5 (42%) responded, of the 8 patients who received a combination of thalidomide and dexamethasone 5 (63%) responded and of the 4 patients who had thalidomide in addition to VAD 2 patients (50%) responded. In 3 patients, thalidomide treatment had to be discontinued because of side effects and 1 patient died before response could be assessed. We conclude that low dose thalidomide is an effective and safe rescue therapy in relapsing or refractory multiple myeloma. Response to thalidomide might be dependent on prognostic parameters and tumor burden. To answer these questions larger prospective studies are necessary.     

Long term use of thalidomide: safe and effective

PURPOSE: To assess the efficacy and safety of high dose thalidomide therapy for longer duration of time in relapsed or refractory Multiple Myeloma (MM) patients. MATERIALS AND METHODS: Twelve relapsed/refractory MM patients (7 Males, 5 Females), who received thalidomide for more than 2 years were selected from the Out Patient Department of Institute Rotary Cancer Hospital (IRCH), AIIMS, India. Patients received thalidomide beginning at a dose of 200 mg/day with fortnightly increment to a maximum dose of 800 mg/day. Patients were assessed for response on the basis of M proteins (MP), bone marrow biopsy with touch preparation and skeletal X-rays. RESULTS: Nine patients tolerated a maximum dose of 800 mg/day whereas three patients were given 600 mg/day. All patients showed > or = 25-50% decline in serum /urine M proteins. Complete response/ near complete response was seen in 50%, partial response in 17% and minimal response (SD) in 34% patients. Median duration of thalidomide therapy was 47 months (range 29-60 months). Currently 11 patients are alive. TOXICITY: Varying degree of constipation and sedation were seen universally. One patient had DVT, which responded to anti-coagulant therapy. Other toxic effects included infections, skin reactions. There was no toxic death. CONCLUSION: Long-term use of thalidomide is safe, effective and feasible. We feel that this is one of few reports describing safety and efficacy of long-term thalidomide in relapsed and refractory MM.     

Use of melphalan,thalidomide, and dexamethasone in treatment of refractory and relapsed multiple myeloma

Twenty-one patients with relapsed and refractory Durie-Salmon stage III multiple myeloma who had either failed at least three previous regimens or presented with poor performance status, neutropenia, or thrombocytopenia were treated with up to four cycles of combination melphalan (50 mg intravenously), thalidomide (titrated to target of 400 mg orally daily), and dexamethasone (40 mg/day orally on d 1 to 4) every 4-6 wk. Maintenance treatment consisting of daily thalidomide and monthly dexamethasone was continued until disease progression. Although generally tolerated, combination melphalan/thalidomide/dexamethasone produced grade 4 neutropenia and thrombocytopenia in 52% and 38% of patients, respectively. Grade 3 nonhematologic toxicities included fatigue (14% of patients), neuropathy/paresthesia (5%), and nausea (5%). Four patients died while on therapy: two from neutropenic complications and two from progressive disease. Melphalan/ thalidomide/dexamethasone was highly active in this poor prognosis population: Serum monoclonal protein reductions > or = 25% occurred in 14 (70%) of 20 evaluable patients, including 1 patient with a complete response and 2 (13%) patients with reductions of 96%. Median progression-free-survival was 270 d (range: 73 to > 787 d) and median overall survival was 382 d. Median progression-free survival (> 420 d) has not been reached among patients responding to melphalan/thalidomide/dexamethasone. These results show that melphalan/thalidomide/dexamethasone therapy is active and generally tolerated in heavily pretreated multiple myeloma patients whose prognosis is otherwise poor.     

Thalidomide for previously untreated indolent or smoldering multiple myeloma.

We conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering (SMM) or indolent multiple myeloma (IMM). Sixteen patients were studied. Thalidomide was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Bone marrow microvessel density (MVD) and angiogenesis grading were estimated using CD34 immunostaining. Six patients had a confirmed response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein. When minor responses (25-49%) decrease in M protein concentration) were included, 11 of 16 patients (69%) responded to therapy. Major grade 3-4 toxicities included two patients with somnolence, and one patient each with syncope and neutropenia. Pre-treatment MVD was not a significant predictor of response to therapy, median MVD 4 and 12 in responders and non-responders respectively, P = 0.09. We conclude that thalidomide has significant activity in the treatment of newly diagnosed SMM/IMM. However, we do not recommend treatment with thalidomide at this stage since some patients with SMM/IMM can be stable for several months or years without any therapy. Additional randomized trials are needed to determine if thalidomide will delay progression to active multiple myeloma.     

Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21

Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per 28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The median follow-up time was 25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease, and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8-10.9) and 13.2 months (95% CI 9.4-21.0), respectively. The median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future development of such an approach in MM.     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

 目的　观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　35例初治及难治复发MM患者,硼替佐米1.1 mg／m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg／d开始逐渐加量至150 mg／d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案。28 d为1个疗程,每例患者至少接受2个疗程以上治疗。达到部分缓解（PR）及以上疗效的患者应用沙利度胺150 mg／d或患者能够耐受的最大剂量维持治疗。采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应。结果　中位随访20个月,35例患者治疗总有效率82.8 ％,其中完全缓解（CR）率48.6 %,良好的部分缓解（VGPR ）率17.1 %,PR率17.1 %。3年预计无进展生存（PFS）和总生存（OS）率分别为60.92 %和72.41 %。达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义（P＝0.004）。初治及难治复发患者客观缓解率（ORR）及OS率差异无统计学意义。Ⅲ～Ⅳ度非血液学毒性主要包括乏力（3／35）、恶心、呕吐（8／35）、便秘（4／35）和周围神经病变（3／35）。Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏（10／35）和血小板减少（8／35）。结论　低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间。     

小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤42例

目的观察小剂量沙利度胺联合含单周地塞米松的VAD方案治疗多发性骨髓瘤（MM）的临床疗效及不良反应。方法给予42例MM患者小剂量沙利度胺（150～200）mg／d联合含单周地塞米松（40mg,口服,第1天至第4天）的VAD方案治疗,28d为1个疗程。4个疗程后进行总体评估。结果总有效率为80．95％（34／42）;其中完全缓解6例,部分缓解20例,进步8例,无效8例。不良反应轻微,患者治疗前后血红蛋白、骨髓浆细胞比例、β2微球蛋白、Karnofsky评分、血肌酐、血免疫球蛋白差异均有统计学意义（均P〈0．001）。结论小剂量沙利度胺联合含单周地塞米松的VAD方案治疗MM有效率高,不良反应轻微,值得临床进一步研究和推广应用。     

小剂量沙利度胺联合COMP方案治疗多发性骨髓瘤的疗效分析

目的观察小剂量沙利度胺联合COMP方案治疗多发性骨髓瘤（MM）的疗效及不良反应,对比其与单纯COMP方案疗效的差异。方法分析42例初治和27例难治复发性MM应用小剂量沙利度胺联合COMP方案的总有效率和不良反应;分析应用两种治疗方案对患者M蛋白、骨髓浆细胞比例和血红蛋白改善情况。结果42例初治MM,单用COMP22例,联合应用小剂量沙利度胺20例,总有效率分别为40．91％和70．00％,两者差异有统计学意义;27例难治复发MM,单用COMP组13例,联合应用14例,总有效率分别为42．86％和84．62％,两者相比差异有统计学意义。应用沙利度胺不良反应轻,患者可以耐受。联合治疗组可以明显提高患者血红蛋白含量、降低血浆M蛋白浓度和骨髓浆细胞比例。结论小剂量沙利度胺联合COMP方案可以提高初治和难治复发MM的总有效率,不良反应轻。     

沙利度胺联合地塞米松诱导治疗初诊多发性骨髓瘤

背景与目的:沙利度胺是治疗复发、难治性多发性骨髓瘤(multiple myeloma,MM)的有效药物,但其在初诊MM诱导治疗中的作用仍不清楚.本研究目的是评价沙利度胺联合地塞米松(thalidomide and dexamethasone,TD)在初诊MM诱导治疗中的治疗效果和不良反应.方法:应用TD方案诱导治疗39例初诊MM.沙利度胺100～300 mg/d,持续口服;地塞米松20～40 mg/d,在奇数疗程的第1～4天、第9～12天和第17～20天口服;在偶数疗程的第1～4天使用,28天为1疗程.并以36例接受VAD方案诱导治疗的临床资料匹配的初诊MM作为历史对照,比较两组的疗效、生存情况和不良反应.结果:TD方案诱导治疗初诊MM的总有效率为71.8%,VAD组为61.1%(P＞0.05).TD组中位无疾病进展生存时间(progression-free survival,PFS)为14个月,VAD组的中位PFS为9个月,两组相比差异无统计学意义(P＞0.05).TD组的中位总生存时间(overall survival,OS)尚未达到,VAD组中位OS为29个月.TD组常见的不良反应有便秘、乏力、头晕、嗜睡等,多为2级以下.VAD组3级以上白细胞减少和血小板降低明显多于TD组(P＜0.05),各种感染的发生率也高于TD组(P＜0.05).结论:TD方案是对初诊MM有效的治疗方案,可以代替VAD方案作为初诊MM的诱导治疗方案.     

沙利度胺对骨髓瘤细胞IL-6及其传导途径的影响

目的　探讨沙利度胺治疗难治复发性多发性骨髓瘤 (MM)的有效机制。方法　用双抗夹心法 (ELISA)动态检测MM患者血清白细胞介素 6 (IL 6 )水平 ,流式细胞仪检测瘤细胞表面IL 6受体 (IL 6R)的表达 ,RT PCR半定量法检测IL 6Rβ亚单位mRNA的表达。 结果　口服 2 0 0mg/d沙利度胺前 ,MM患者血清IL 6水平为 5 6 4.8± 319.4ng/L ,瘤细胞表面IL 6R阳性率为 33.6 % ;口服 2 0 0mg/d沙利度胺后第 14天 ,IL 6水平为 5 6 0 .3± 414.8ng/L ,瘤细胞表面IL 6R阳性率为 31.8% ,分别与口服沙利度胺前比较 ,差异无显著性 (P >均 0 .0 5 )。口服 40 0mg/d沙利度胺第 14,2 8,42 ,5 6 ,84天 ,IL 6水平分别为 5 16 .7± 131.9、42 6 .7± 180 .4、387.9± 187.4、35 0 .1± 85 .5和 2 12 .3± 92 .5ng/L ,瘤细胞表面IL 6R阳性率分别为 2 8.5 %、2 4.3%、2 1.3%、12 .6 %和 10 .1% ,均分别低于口服 2 0 0mg/d沙利度胺前IL 6水平或瘤细胞表面IL 6R阳性率 (P <0 .0 5或P <0 .0 1) ;口服 2 0 0mg/d沙利度胺前及口服第 14天的IL Rβ亚单位mRNA比值分别为 7.8和 6 .9,二者差异无显著性 (P >0 .0 5 ) ;口服沙利度胺 40 0mg/d第 14,2 8天IL Rβ亚单位mRNA的比值分别为 5 .3和 2 .7,与口服 2 0 0mg/d沙利度胺前的比较 ,差异有显著性 (P     

Analysis of the Efficacy of Thalidomide Plus Dexamethasone-Based Regimens in Patients With Relapsed/Refractory Multiple Myeloma Who Received Prior Chemotherapy,Including Bortezomib and Lenalidomide: KMM-166 Study

BackgroundFor patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM).Patients and MethodsWe conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide.ResultsIn 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities.ConclusionThalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.     

Thalidomide and dexamethasone combination for refractory multiple?myeloma

Background:Thalidomide is effective in approximately 30%of patients with refractory multiple myeloma. Dexamethasone is active in25% of patients with disease resistant to alkylating agents. Weinvestigated the combination of thalidomide with dexamethasone as salvagetreatment for heavily pretreated patients with multiple myeloma, in order toassess its efficacy and toxicity. Patients and methods:Forty-four patients with refractory myelomawere treated with thalidomide, 200 mg p.o. daily at bedtime, with doseescalation to 400 mg after 14 days, and dexamethasone, which was administeredintermittently at a dose of 20 mg/m² p.o. daily for four days onday 1–4, 9–12, 17–20, followed by monthly dexamethasone forfour days. Patients' median age was 67 years. All patients wereresistant to standard chemotherapy, 77% were resistant todexamethasone-based regimens and 32% had previously received high-dosetherapy. Results:On an intention-to-treat basis twenty-four patients(55%) achieved a partial response with a median time to response of 1.3months. The thalidomide and dexamethasone combination was equally effectivein patients with or without prior resistance to dexamethasone-based regimensand in patients with or without prior high-dose therapy. Toxicities were mildor moderate and consisted primarily of constipation, morning somnolence,tremor, xerostomia and peripheral neuropathy. The median time to progressionfor responding patients is expected to exceed 10 months and the mediansurvival for all patients is 12.6 months. Conclusion:The combination of thalidomide with dexamethasoneappears active in patients with refractory multiple myeloma. If this activityis confirmed, further studies of this combination as second-line treatment forpatients resistant to conventional chemotherapy, and as primary treatment forpatients with active myeloma, should be considered.     

Possible multiple myeloma dedifferentiation following thalidomide therapy: a report of four cases

Thalidomide has been shown to be effective in approximately 30% of patients with refractory or advanced multiple myeloma (MM). Here we report on 4 cases of patients treated with thalidomide for refractory MM showing dedifferentiation of the neoplasm. In these cases thalidomide treatment despite reduction of M-component-was followed by disease progression and a very poor clinical outcome which was paralleled by bone marrow plasmacytosis showing marked signs of dedifferentiation, inducing us to speculate on a potential role of thalidomide on dedifferentiation of myeloma cells. In our opinion, a possible dedifferentiation of MM should therefore be taken into account in MM patients treated with thalidomide when clinical course deteriorates despite reduction of M-component.