Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach

We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone marrow homing, possible mechanisms of extramedullary spread, and prognosis and response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to 20% at relapse. The current notion that EMPs are more frequent after treatment with novel agents remains to be proven, especially considering that different patterns of disease recurrence can emerge as patients live longer in the era of novel drugs. Bone marrow genetic abnormalities are not associated with extramedullary spread per se, which also suggests that microenvironmental interactions are key. Possible mechanisms of extramedullary spread include decreased adhesion molecule expression and downregulation of chemokine receptors. EMPs usually show plasmablastic morphology with negative CD56 expression. High-dose therapy with autologous stem-cell transplantation (ASCT) can overcome the negative prognostic impact of extramedullary disease in younger selected patients. EMPs do not typically respond to thalidomide alone, but in contrast, responses to bortezomib have been reported. The incidence of EMPs in patients with MM is high and is associated with poor outcome in patients treated conventionally. A potential first-line treatment option seems to be a bortezomib-containing regimen followed by ASCT, whenever possible. Experimental studies on the mechanisms of myeloma cell adhesion, myeloma growth at extramedullary sites, and drug sensitivity are priorities for this area of continuing therapeutic challenge.     

Longitudinal Real-World Neuropathy and Patient-Reported Outcomes With Bortezomib and Lenalidomide in Newly Diagnosed Multiple Myeloma

BackgroundPeripheral neuropathy is a common treatment-emergent side effect during the treatment of newly diagnosed multiple myeloma. Although bortezomib is most commonly implicated, real-world data suggest that lenalidomide and dexamethasone (VRd) and autologous stem cell transplantation (ASCT) may also contribute to neuropathy and health-related quality of life (HRQoL).MethodsThe Multiple Myeloma Research Foundation (MMRF) CoMMpass Registry was queried for all patients who received frontline VRd or bortezomib, cyclophosphamide and dexamethasone (VCd). Incidence of neuropathy and patient-reported HRQoL outcomes over the first 12 months after diagnosis were compared between patients receiving VRd or VCd with or without early ASCT before 6 months.ResultsThere were 368 and 191 patients treated with VRd and VCd, respectively. VRd with early ASCT was associated with worse grade 1 neuropathy compared to VRd without early ASCT, as well as compared to VCd with early ASCT. There were no differences in neuropathy between VRd and VCd without early ASCT, and no differences in grade ≥2 neuropathy. There were significant improvements in HRQoL between baseline and 12 months in both VRd and VCd cohorts, regardless of early ASCT. Development of neuropathy was not associated with decrements in progression-free survival or overall survival.ConclusionsIn this longitudinal database analysis, there were no differences in grade ≥2 neuropathy between VRd and VCd frontline induction, and overall HRQoL significantly improved across all cohorts. However, differences in grade 1 neuropathy between VRd and VCd induction suggest that lenalidomide and high-dose melphalan may augment the risk of neuropathy in newly diagnosed multiple myeloma.     

Central nervous system niche involvement in the leukemia

Central nervous system (CNS) impairment is commonly involved in leukemia, as it can be observed upon onset or relapse of the disease. It is associated with poor prognosis and is a challenging clinical problem. The objective of this paper was to provide a characterization of the CNS niche in leukemia, to elucidate the culprits of CNS involvement, including diagnostic micro RNAs (miRs) and early leukemia prognosis. CNS niche is a proper location for homing of leukemic stem cells, thus representing a candidate target in the treatment of leukemia. Recent advances in the study of leukemia hallmarks have enlightened miRs as novel biomarkers for diagnosis and detection of CNS involvement in leukemia, thus providing the opportunity to develop novel therapeutic approaches. Given the importance of prognosis and early diagnosis of CNS involvement in leukemias as well as the severe side effects of current treatments, diagnostic and therapeutic approaches should focus on identification and inhibition of the factors contributing to CNS involvement, including CXCR3, P-selectin glycoprotein ligand-1 and MCP1. MiRs such as miR-221 and miR-222 are emerging as potential tools for an innovative non-invasive therapy of CNS in leukemia affected patients.     

Panobinostat: A Review in Relapsed or Refractory Multiple Myeloma

Oral panobinostat (Farydak®), a potent nonselective histone deacetylase inhibitor, is approved in several countries for use in combination with bortezomib and dexamethasone in patients with multiple myeloma (MM) [USA] or relapsed and/or refractory MM (EU) who have received at least two prior treatment regimens, including bortezomib and an immunomodulatory drug (IMiD). In a pivotal phase III trial (PANORAMA 1) in patients with relapsed or relapsed and refractory MM who had received one to three previous lines of therapy, progression-free survival (PFS) was significantly prolonged with panobinostat plus bortezomib and dexamethasone compared with placebo plus bortezomib and dexamethasone. The significantly favourable effect of panobinostat- versus placebo-based treatment on PFS was also observed in a subgroup analysis of patients who had previously received an IMiD, bortezomib plus an IMiD, or at least two lines of treatment including bortezomib and an IMiD. Panobinostat plus bortezomib and dexamethasone had a generally manageable tolerability profile, with the most frequent grade 3–4 adverse events being myelosuppression, diarrhoea, asthenia or fatigue, peripheral neuropathy and pneumonia. Thus, panobinostat, in combination with bortezomib and dexamethasone, is a useful addition to the available treatment options for patients with relapsed or refractory MM.     

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.     

Current developments in immunotherapy in the treatment of multiple myeloma

Multiple myeloma (MM) is the second most common hematologic malignancy and represents approximately 10% of all hematological neoplasms. Standard therapy consists of induction therapy followed by high‐dose chemotherapy and autologous stem cell transplantation (ASCT) or, if ASCT cannot be performed, standard doublet, triplet, or quadruplet, novel agent–containing induction treatment until progression. Although MM is still regarded as mostly incurable by current standards, the development of several novel compounds, combination therapies, and immunotherapy approaches has raised great hopes about transforming MM into an indolent, chronic disease and possibly achieving a cure for individual patients. Several new inhibitory and immunological agents have been approved or are under intensive investigation and may lead to new therapeutic options for patients with relapsed/refractory MM, for patients ineligible for ASCT, and for patients after ASCT. Especially in the field of immunotherapy, including monoclonal antibodies, checkpoint inhibition, and chimeric antigen receptor T cells, current advances are rapid and highly promising. This review aims to summarize the newest and most promising immunotherapeutic agents for MM, their clinical efficacy, their adverse event (AE) profiles, and the ways in which these AEs can best be overcome or avoided. Cancer 2018;124:2075‐85 . © 2018 American Cancer Society.     

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

Background

Immunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes.

Design and methods

Seventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group.

Results

Median age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT.

Conclusions

Despite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.     

Impact of bortezomib on bone health in myeloma: A review of current evidence

Bone disease is a key feature in multiple myeloma (MM) and can have a substantial impact on patient morbidity and quality-of-life. The pathogenesis of lytic bone disease in MM is complex and associated with increased osteoclast activity and impaired osteoblast function. Lytic lesions rarely heal in MM; however, the proteasome inhibitor bortezomib has been linked to increased bone formation and osteoblastic activity. Various clinical studies have reported a positive effect of bortezomib on bone health, including fewer bone disease-related MM progression events, increases in bone volume, and improvements in osteolytic lesions. Alkaline phosphatase (total and bone isoenzyme), a marker of bone formation, is increased during bortezomib treatment; the degree of increase may be associated with treatment response. Bortezomib is associated with a reduction in Dickkopf-1, an inhibitor of osteoblast function. Increases of other bone-formation markers and decreases of bone-resorption markers, have also been observed. These clinical effects are supported by preclinical data suggesting bortezomib is associated with an increase in bone formation and osteoblast numbers/activity, arising from direct effects of bortezomib and proteasome inhibition. As reviewed here, a growing body of evidence indicates that bortezomib exerts a positive effect on bone metabolism in MM and has a bone anabolic effect.     

IgD型多发性骨髓瘤的诊治现状及展望

IgD型多发性骨髓瘤（IgD multiple myeloma，IgD MM）是多发性骨髓瘤（multiple myeloma，MM）中一种罕见类型，以年轻男性患者居多。主要表现为高钙血症、肾衰竭、贫血、骨损害、髓外浸润和系统性淀粉样变性等，具有侵袭性高，预后较差的特点。近年来，随着免疫调节剂（沙利度胺、来那度胺）、蛋白酶抑制剂（硼替佐米）等药物以及自体造血干细胞移植（autologous stem cell transplantation，ASCT）的应用，IgD型MM的预后得到明显改善。新一代蛋白酶体抑制剂、CD38单克隆抗体、组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor,HDACI）、新型免疫治疗技术等治疗方法也为IgD型MM 的治疗提供了新的方向。目前关于IgD型MM的相关报道较少，本文就IgD型MM的临床特点、诊断、治疗、预后及新药研究现状进行如下综述。     

新药时代多发性骨髓瘤的维持治疗:第57届美国血液学会年会报道

近年来,多发性骨髓瘤(MM)的新药治疗发展迅速,但患者在目前已有的治疗条件下,疾病仍然在缓解与复发中反复.越来越多的证据表明,MM患者在最终治疗后接受长期维持治疗有助于抑制残留病灶,延长缓解期,并延迟复发.对于接受自体干细胞移植(ASCT)的MM患者,来那度胺维持治疗可以提高无进展生存(PFS)率,但并不延长总生存(OS)时间.对于不适合接受ASCT的MM患者,一项大型Ⅲ期临床研究对持续来那度胺加低剂量地塞米松治疗与标准的固定疗程美法仑、 泼尼松加沙利度胺治疗进行了比较,中期分析结果显示前者的PFS及OS优于后者.其他试验也就ASCT患者沙利度胺及硼替佐米维持治疗进行了研究,这两种药物也可作为不适合ASCT患者的维持治疗.然而,关于最佳治疗方案及持续时间等问题还需要通过前瞻性临床试验得出结论,但目前一致认为,维持治疗应该作为MM的常规治疗.文章对第57届美国血液学会(ASH)年会报道的MM维持治疗的相关研究进行回顾分析,以明确维持治疗在MM治疗中的作用.     

Central nervous system metastases in women after multimodality therapy for high risk breast cancer

Background: Central nervous system (CNS) relapse is increasing in breast cancer. This increase may reflect altered failure patterns from adjuvant therapy, more effective systemic therapy with improved control in non-CNS sites, or a resistant breast cancer subtype.Methods: To determine the factors associated with clinical CNS relapse, we examined response to neoadjuvant chemotherapy (chemosensitivity), time to relapse and sites of relapse in a cohort of 140 patients without evidence of metastasis at presentation.Results: At 5 years (interquartile range 3–6 years), 44 (31%) patients developed distant metastases, including 13 with CNS metastases. CNS relapse was early (median 24 months after diagnosis) and associated with relapse in bone and liver, suggesting hematogenous dissemination. Those with CNS relapse were younger at diagnosis (40 versus 49 years) and more likely to have lymphovascular invasion in the primary tumor compared with non-CNS metastases. Response to neoadjuvant chemotherapy was not different (69% versus 73% response rate) between the two groups. Extent of residual disease after chemotherapy was strongly associated with relapse outside the CNS but not CNS relapses. The CNS was an isolated or dominant site of metastasis in 8 of 13. Despite treatment, most patients with CNS involvement died of neurologic causes a median of 6 months later.Conclusion: Breast cancers that develop CNS metastases differ from those that develop metastases elsewhere. Both tumor behavior and reduced chemotherapy accessibility to the CNS may contribute to increased CNS involvement in breast cancer patients treated with multimodality therapy.     

Bortezomib,thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

BACKGROUND:

This single‐center retrospective study determined the efficacy of bortezomib, thalidomide, and dexamethasone (BTD) as induction for patients with multiple myeloma (MM) who were eligible for autologous stem cell transplantation (ASCT).

METHODS:

Patients with symptomatic MM who had received BTD induction before stem cell collection at Winship Cancer Institute were included. BTD induction comprised up to 8 3‐week cycles of bortezomib 1.3 mg/m² on Days 1, 4, 8, and 11; thalidomide 100 mg daily; and dexamethasone 40 mg on Days 1 through 4 and Days 9 through 12. Stem cell mobilization involved granulocyte‐colony–stimulating factor and/or cyclophosphamide. Response was assessed according to European Group for Blood and Marrow Transplantation criteria.

RESULTS:

Review of medical records identified 44 eligible patients (34 patients who were treated in the front‐line setting and 10 patients who were treated for recurrent disease) who received a median of 4 BTD cycles. The overall response rate (ORR) was 91%, which included a greater than or equal to very good partial response (≥VGPR) rate of 57% (including 20% stringent complete responses/complete response [sCR/CR] rate). In front‐line patients, the ORR was 94%, which included a 56% ≥VGPR rate (24% sCR/CR). The median CD34‐positive stem cell collection was 10.67 × 10⁶/kg. The ORR after ASCT in 34 patients who were evaluable for response was 100%, including a 76% ≥VGPR rate (53% sCR/CR). Among all 44 patients, the median progression‐free survival (PFS) was 27.4 months. The median overall survival (OS) was not reached after a median follow‐up of 25 months, and the 2‐year OS rate was 82%. There were no significant differences in PFS (27.4 months vs 23.5 months) or in 2‐year survival (80% vs 90%) between patients who did and did not undergo ASCT, respectively. Twenty patients (45%) developed neuropathy, including 4 (9%) with grade 3 neuropathy episodes, and 1 patient developed deep vein thrombosis.

CONCLUSIONS:

BTD was highly effective and well tolerated as induction for MM patients who were eligible for ASCT. Long‐term outcomes appeared to be similar with or without ASCT consolidation. Cancer 2010. © 2010 American Cancer Society.     

Treatment of Multiple Myeloma: A Comprehensive Review

Multiple myeloma (MM) is a neoplastic plasma cell disorder that results in end-organ damage (hypercalcemia, renal insufficiency, anemia, or skeletal lesions). Patients should not be treated unless they have symptomatic (end-organ damage) MM. They should be classified as having high-risk or standard-risk disease. Patients are classified as high risk in the presence of hypodiploidy or deletion of chromosome 13 (del[13]) with conventional cytogenetics, the presence of t(4:14), t(14;16), t(14;20) translocations or del(17p) with fluorescence in situ hybridization. High-risk disease accounts for about 25% of patients with symptomatic MM. If the patient is deemed eligible for an autologous stem cell transplantation (ASCT), 3 or 4 cycles of lenalidomide and low-dose dexamethasone, or bortezomib and dexamethasone, or thalidomide and dexamethasone are reasonable choices. Stem cells should then be collected and one may proceed with an ASCT. If the patient has a complete response or a very good partial response (VGPR), the patient may be followed without maintenance therapy. If the patient has a less than VGPR, a second ASCT is encouraged. If the patient is in the high-risk group, a bortezomib-containing regimen to maximum response followed by 2 additional cycles of therapy is a reasonable approach. Lenalidomide and lowdose dexamethasone is another option for maintenance until progression. If the patient is considered ineligible for an ASCT, then melphalan, prednisone, and thalidomide is suggested for the standard-risk patient, and melphalan, prednisone, and bortezomib (MPV) for the high-risk patient. Treatment of relapsed or refractory MM is covered. The novel therapies—thalidomide, bortezomib, and lenalidomide—have resulted in improved survival rates. The complications of MM are also described. Multiple myeloma is a plasma cell neoplasm that is characterized by a single clone of plasma cells producing a monoclonal protein (M-protein). The malignant proliferation of plasma cells produces skeletal destruction that leads to bone pain and pathologic fractures. The M-protein might lead to renal failure, hyperviscosity syndrome, or through the suppression of uninvolved immunoglobulins, recurrent infections. Anemia and hypercalcemia are common complications.     

Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL)

High Ki-67 is strongly associated with the risk of CNS relapse in patients with mantle cell lymphoma. Two-year incidence of CNS relapse in patients with Ki-67 ≥ 30 exceeds 25%. The incidence was not decreased by rituximab, high-dose cytarabine, high-dose methotrexate or consolidative ASCT. Development of new prophylactic strategies for CNS involvement is mandatory in patients with high Ki-67.BackgroundCentral nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.Patients and methodsA total of 608 patients (median age, 67 years; range 22–92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.ResultsNone of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2–141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9–19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5–39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4–4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.     

Treatment of extensive B-cell lymphoma in children: studies of the French Pediatric Oncology Society

Since 1981 in the French Pediatric Oncology Society, a multidrug intensive-pulsed chemotherapy was proposed for bad prognosis B-cell lymphomas (stage II ORL, III and IV) and for B acute lymphocytic leukemias (B-ALL). Between 1981 and 1984, the nine-drug regimen was based on high-dose cyclophosphamide, high-dose methotrexate and cytosine arabinoside in continuous infusion (regimen LMB-81). No irradiation was performed. CNS prophylaxis was made by high-dose methotrexate and by intrathecal injections. No debulking surgery was recommended. Since 1984, considering the high rate of continuous remission, some modifications were made for reducing the duration and toxicity of the treatment of most B-cell lymphomas without CNS involvement (regimen LMB-84). For B-cell lymphomas with CNS involvement and B-ALL, an intensive high-dose multidrug combination was proposed (regimen LMB-86). Between 1981 and 1984, 153 children (stage II ORL: 6%, III: 63%, IV: 31%) were treated with the LMB-81 regimen. The overall disease-free survival rate is 69%. No relapse occurred after 12 months. Only two CNS relapses were observed. Among stage IV, a worse prognosis was associated with initial CNS involvement (disease free survival: 19%). On the contrary, bone marrow involvement was not an adverse prognostic factor. With the LMB-84, the overall disease free survival rate is 74%. A noteworthy reduction of toxicity is observed.     

非霍奇金淋巴瘤中枢神经系统累及的诊断和预防

 非霍奇金淋巴瘤（NHL）患者中枢神经系统（CNS）累及预后不良,其中位生存期2～6个月。与NHL CNS累及相关参数是年轻、进展期、累及结外部位数、乳酸脱氢酶（LDH）增高和国际预后指标（IPI）积分。最有希望的治疗为自体造血干细胞移植,可延长中数生存期10～26个月。处于CNS侵袭高危状态的某些NHL亚型患者需要早期进行CNS预防,如伯基特淋巴瘤（BL）和淋巴母细胞淋巴瘤（LBL）。弥漫性大B细胞淋巴瘤（DLBCL）初期治疗时是否需应用CNS预防久有争议,因为它属于CNS累及（≈5 ％）的低危群体。危险模式的确定有助于预示NHL的CNS复发。     

Efficacy and safety of bortezomib in patients with plasma cell leukemia

BACKGROUND: The prognosis of patients with plasma cell leukemia (PCL), an aggressive variant of multiple myeloma (MM), is usually poor. Bortezomib is the first proteasome inhibitor approved for the treatment of advanced MM. Currently available information regarding the role of bortezomib in PCL is scanty and derives from anecdotal, single-case reports. METHODS: The authors conducted a retrospective survey of unselected Italian patients with primary or secondary PCL who were treated with bortezomib outside of clinical trials. Twelve evaluable patients were recorded who had received bortezomib for 1 to 6 cycles as either a single agent or variously combined with other drugs. Three patients were treated with bortezomib as frontline therapy, and 9 patients received bortezomib after 1 to 4 lines of chemotherapy, including autologous stem cell transplantation and thalidomide. RESULTS: According to the International uniform response criteria of the International Myeloma Working Group, 5 partial responses (defined as a reduction in M-protein of >50%), 4 very good partial responses (defined as a reduction of >90% in M-protein), and 2 complete responses (defined as negative immunofixation) were achieved, for a response rate of 92%. Responses did not appear to be influenced by previous treatments or by other clinical or biologic parameters, including chromosome 13 deletion or the combination of bortezomib with other drugs. The median progression-free and overall survivals after bortezomib were 8 months and 12 months, respectively. At the time of last follow-up, 8 patients were alive 6 to 21 months after treatment with bortezomib, 4 of whom were in very good partial or complete responses. Grade 3/4 hematologic or neurologic toxicities (graded according to the Common Terminology Criteria for Adverse Events [CTCAE; version 3]) were reported to occur in 9 patients and 1 patient, respectively, whereas 6 patients experienced possible or documented infections. CONCLUSIONS: Bortezomib appears to be an effective drug for PCL that could significantly improve the usually adverse clinical outcome of these patients.     

Prolonged survival after second autologous transplantation and lenalidomide maintenance for salvage treatment of myeloma patients at first relapse after prior autograft

Autologous stem cell transplantation (ASCT) as part of the primary therapy in multiple myeloma (MM) is standard practice. In contrast, the role of a second ASCT (ASCT2) and subsequent lenalidomide maintenance for relapsed disease remains unclear. In this study, we analysed 86 consecutive MM patients with a first relapse after prior ASCT receiving either a second ASCT or conventional chemotherapy. After a median follow‐up of 37.7 months since first relapse, 54 (62.8%) patients were still alive and 29 (33.7%) without progression. Sixty‐one (71.0%) patients received ASCT2 and had better progression‐free survival (PFS) (30.2 versus 13.0 mo; P = .0262) and overall survival (OS) rates (129.6 versus 33.5 mo; P = .0003) compared with 25 (29.0%) patients with conventional treatment. Patients relapsing later than 12 months after ASCT1 benefitted from a second ASCT with better PFS2 (P = .0179) and OS2 (P = .0009). Finally, lenalidomide maintenance after ASCT2 was associated with longer PFS (41.0 vs 21.6 mo; P = .0034) and better OS (not yet reached vs 129.6 mo; P = .0434) compared with patients without maintenance. Our data suggest that a second ASCT and lenalidomide maintenance given at first relapse in MM after prior ASCT are associated with better survival rates.     

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。     

硼替佐米治疗浆细胞病患者临床不良反应分析

目的:了解硼替佐米不良反应的特点,为临床使用提供参考.方法:通过对2007年至2009年之间临床确诊的浆细胞病患者使用硼替佐米的观察,收集不良反应报告表进行统计分析.结果:硼替佐米在治疗浆细胞病患者过程中不良反应发生率为乏力12.9%、腹泻35.5%、血小板减少16.1%、带状疱疹19.4%、外周神经病16.1%.结论:硼替佐米在临床应用中易出现不良反应,但严重的死亡病例未见.应进一步加强对硼替佐米临床应用过程中不良反应的监测,积极开展其不良反应发生机理的研究,促进该药品安全性的再评价.