Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma

Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR]=1.4), high-grade lymphoma (OR=2.3), and unclassified lymphoma (OR=2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Drs Gibson and Schuman are in the Department of Epidemiology, University of Minnesota, Minneapolis, MN, USA. Dr Burmeister is in the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415C, Bethesda, MD 20892, USA. This work was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

Smoking and the risk of leukemia, lymphoma, and multiple myeloma (Sweden)

While several epidemiologic studies have indicated a link between smoking and the risk of developing hema-tolymphoproliferative cancers (chiefly leukemias, lymphomas, and multiple myelomas), in particular myeloid leukemia, the role of tobacco in the etiology of these neoplasms remains unclear. To evaluate the potential impact of tobacco use on development of leukemia, lymphoma, and multiple myeloma, we conducted a cohort study of 334,957 Swedish construction workers using prospectively collected exposure-information with complete long-term follow-up. A total of 1,322 incident neoplasms occurred during the study period, 1971-91. We found no significant association between smoking status, number of cigarettes smoked, or duration of smoking and the risk of developing leukemias, lymphomas, or multiple myeloma. There was a suggestion of a positive association between smoking and the risk of developing Hodgkin's disease, although the rate ratios were not significantly elevated, except for young current smokers. No positive dose-risk trends emerged. Our study provides no evidence that smoking bears any major relationship to the occurrence of leukemias, non-Hodgkin's lymphomas, or multiple myeloma.     

Obesity and multiple myeloma

An exploratory study was conducted of common clinical conditions as predictors of subsequent cancer in 143,574 outpatients of a health maintenance organization (in California, USA). An association was noted between obesity, diagnosed in 14,388 patients, and the subsequent development of multiple myeloma (MM) in up to 21 years (33 cases observed, 21.3 expected based on the experience of the entire cohort; standardized morbidity ratio=1.55, 95 percent confidence interval [CI]=1.06–2.17). This association was evaluated further in a second cohort of 163,561 multiphasic-checkup examinees followed up for as many as 24 years. Body mass index (BMI) at entry examination was associated positively with the incidence of MM in White men (e.g., relative risk [RR]=1.07, CI=1.01–1.15 per unit increase in BMI; and RR=1.68, CI=0.75–3.78, comparing the highest with lowest quartile). This association was absent in White women, partially confirmed in Black men and women (BMI quartiles two, three, and four showed higher risk than quartile one), and not explained by the presence of diabetes mellitus. The association was reduced or absent with BMI based on reported greatest adult-weight, and in White women was inverse with BMI based on reported lowest adult-weight. Among subjects with more than one checkup, increased risk was associated directly with weight loss among White men and associated inversely with weight gain among Black women. These findings suggest that body build or nutritional status may be involved in the development of MM by mechanisms that are presently unknown. If increased weight is a causal factor, weight loss occurs later after the disease process begins.This research was supported by Grant R35 CA 49761 from the US National Cancer Institute.     

Animal-related occupations and the risk of leukemia,myeloma, and non-Hodgkin's lymphoma in Canada

Objective: There is some evidence to suggest that workers in animal-related occupations are at increased risk of developing lymphohematopoietic cancers. This study aimed to examine the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma associated with occupational exposure to animals. Methods: We used data from a multi-site, population-based case–control study using mailed questionnaires which had taken place in eight of ten Canadian provinces, during 1994–1998. There were 1023 leukemia cases, 1577 NHL cases, and 324 multiple myeloma cases (all histologically confirmed) and 4688 population-based controls. Animal-related occupations were identified from a lifetime occupational history. Subjects in animal-related jobs were compared with others using logistic regression for the risk of leukemia, NHL, and multiple myeloma. Results: Compared to subjects without occupational exposure to animals, occupational exposure to beef cattle increased the risks of leukemia (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.2–3.3) and NHL (OR 1.8, 95% CI 1.1–2.9). No other animal exposure was consistently associated with risk of lymphohematopoietic cancer. An unexpected protective association was observed between work as a fisherman and leukemia (OR 0.4, 95% CI 0.2–0.8) and NHL (OR 0.6, 95% CI 0.4–0.9). Conclusions: This population-based case–control study found that those individuals working in occupations associated with beef cattle are at increased risk for developing leukemia and lymphoma while those working in occupations requiring the handling of fish are at decreased risk of leukemia and lymphoma.     

The evolving role of maintenance therapy following autologous stem cell transplantation in multiple myeloma

ABSTRACT

Introduction: Maintenance therapy after autologous transplantation is a standard of care in newly diagnosed myeloma. However, there is no universal answer to the question of which maintenance strategy should be pursued after ASCT?

Areas covered: We conducted a MEDLINE search using the medical subject headings ‘multiple myeloma’, ‘autologous transplantation’ and ‘maintenance’ to identify available data from clinical trials on the role of different maintenance strategies after autologous transplantation for the newly diagnosed disease.

Expert opinion: A large meta-analysis demonstrated that lenalidomide prolongs progression-free and overall survival after autologous transplantation compared to observation/placebo. Further trials confirmed that lenalidomide maintenance increases rates of high-quality responses and one study demonstrated that lenalidomide maintenance improves outcomes regardless of cytogenetic risk. Although lenalidomide can cause side effects and is associated with an increased risk of second primary malignancies, its benefits outweigh the mentioned risks. The proteasome inhibitors ixazomib and bortezomib may partially overcome the negative effects of high-risk cytogenetics. Future trials will combine different agents and monoclonal antibodies during maintenance and will investigate whether minimal residual disease status can guide maintenance duration.     

Minimal residual disease detection in lymphoma and multiple myeloma: impact on therapeutic paradigms

Early identification of patients at high risk of relapse is a major goal of current translational research in oncohematology. Minimal residual disease (MRD) detection by polymerase chain reaction-based methods is currently part of the routine clinical management of patients with acute lymphoblastic leukemia. However, the current knowledge indicates that it is also a useful prognostic tool in several mature lymphoproliferative disorders. Its utility is currently well established in follicular lymphoma, mantle cell lymphoma, and multiple myeloma. In some of these entities, clinical trials employing MRD as a decision-making tool are currently ongoing. In the present review, we will discuss the 'state of the art' of MRD evaluation in these three neoplasms with the ultimate aim of providing critical take-home messages for clinicians working in the field. Moreover, we will outline the role of MRD detection in the design of future clinical trials.     

Bortezomib in multiple myeloma and lymphoma: a systematic review and clinical practice guideline

Questions

1. In patients with multiple myeloma, Waldenström macroglobulinemia, or lymphoma, what is the efficacy of bortezomib alone or in combination as measured by survival, quality of life, disease control (for example, time to progression), response duration, or response rate?
2. What is the toxicity associated with the use of bortezomib?
3. Which patients are more or less likely to benefit from treatment with bortezomib?

Perspectives

Evidence was selected and reviewed by two members of the Hematology Disease Site Group and by methodologists from the Program in Evidence-based Care (pebc) at Cancer Care Ontario. The practice guideline report was reviewed and approved by the Hematology Disease Site Group, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to practitioners throughout Ontario to obtain their feedback.

Outcomes

Outcomes of interest were overall survival, quality of life, response rates and duration, and rates of adverse events.

Methodology

A systematic search was conducted of the medline, embase, HealthStar, cinahl, and Cochrane Library databases for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. Those recommendations were appraised by a sample of practitioners in Ontario and modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body w theithin pebc.

Results

The literature review found one randomized controlled trial (rct)—the only published rct of bortezomib in relapsed myeloma. A number of phase ii studies were also retrieved, including a randomized phase ii study. No randomized trials were retrieved for lymphoma.The rct found bortezomib to be superior to high-dose dexamethasone for median time to progression and 1-year survival in patients with relapsed myeloma, although grade 3 adverse events were more common in the bortezomib arm. Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation.

Practice Guideline

This evidence-based series applies to adult patients with myeloma, Waldenström macroglobulinemia, or lymphoma of any type, stage, histology, or performance status.

Recommendations

Based on the results of a large well-conducted rct, which represents the only published randomized study in relapsed myeloma, the Hematology Disease Site Group (dsg) offers the following recommendations:

• For patients with myeloma refractory to or relapsing within 1 year of the conclusion of initial or subsequent treatment or treatments, including autologous stem-cell transplantation, and who are candidates for further chemotherapy, bortezomib is recommended as the preferred treatment option.
• Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation. The dsg is aware that thalidomide, alkylating agents, or repeat transplantation may also be options for these patients. However, evaluation of these other options is beyond the scope of this practice guideline.
• For patients with myeloma relapsing at least 1 year after the conclusion of alkylating agent–based chemotherapy who are candidates for further chemotherapy, further treatment with alkylating agent–based chemotherapy is recommended.
• Evidence is insufficient to support the use of bortezomib in patients with non-Hodgkin lymphoma or Waldenström macroglobulinemia outside of clinical trials.

Qualifying Statements

Limited evidence supports the appropriateness of a specific time-to-relapse period as being indicative of treatment-insensitive disease. The 1-year threshold provided in the foregoing recommendations is based on the opinion of the Hematology dsg.For specific details related to the administration of bortezomib therapy, the dsg suggests that clinicians refer to the protocols used in major trials. Some of those details are provided here for informational purposes.

Dosage

Bortezomib 1.3,g/m² is given as a rapid intravenous bolus over 3–5 seconds on days 1, 4, 8, and 11 of a 21-day cycle; a minimum of 72 hours between doses is required to allow for recovery of normal proteasome function. Vital signs should be checked before and after each dose. A complete blood count is recommended before each dose, with blood chemistries (including electrolyte and creatinine levels) monitored at a minimum on days 1 and 8 of each cycle. The dose of bortezomib should be reduced or held immediately upon development of painful neuropathy, as described in the product monograph; dose modification may also be required for peripheral sensory neuropathy without pain or for other toxicities. Most toxicities are reversible if dose modification guidelines are followed.

Response to Treatment

Responses are usually apparent by 6 weeks (2 cycles). For patients achieving complete remission (determined by negative electrophoresis and immunofixation), bortezomib should be given for 2 additional cycles beyond the date of confirmed complete remission. In patients with progressive disease after 2 cycles or stable disease after 4 cycles, dexamethasone added to the bortezomib regimen (20 mg by mouth the day of and the day after each bortezomib dose) may produce an objective response. Bortezomib (with or without dexamethasone) should be continued in patients showing benefit from therapy (excluding those in complete remission) unless disease progression or significant toxicity is observed. Therapy should be discontinued in patients who do not respond to bortezomib alone if disease progression is seen within 2 cycles of the addition of dexamethasone.The Hematology dsg recognizes that thalidomide is an active agent in multiple myeloma patients who have relapsed after autologous stem-cell transplantation or who are refractory to alkylating agent–based chemotherapy. To date, no reported rcts have evaluated thalidomide in this role, and specifically, no trials have compared thalidomide with bortezomib. Given these limitations, the members of the Hematology dsg regard thalidomide or bortezomib as therapy alternatives to dexamethasone.     

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.     

维持治疗方案改善多发性骨髓瘤患者的生存与预后

目的:分析多发性骨髓瘤（multiple myeloma,MM）患者维持治疗及方案与无进展生存期（PFS）、总生存期（OS）的联系,为临床指导治疗。方法:回顾性分析2015年03月至2020年09月在我院住院治疗的所有MM患者,总结其随访结果,分析是否维持治疗以及维持治疗方案对PFS以及OS的影响。结果:维持治疗的患者PFS与OS均优于不维持治疗者（P=0.000,P=0.002）。以来那度胺为主的维持治疗方案疗效最佳（PFS:P=0.000,OS:P=0.005）。单因素分析结果显示MM ISS分期与PFS有关(P=0.040),多因素分析结果提示MM ISS分期和是否维持治疗及维持治疗方案均对PFS有显著影响(P=0.033,P=0.017,P=0.027),是否维持治疗对OS有影响(P=0.016)。结论:维持治疗有利于MM患者生存。以来那度胺为主的维持治疗方案疗效佳,可作为首选。     

Pesticide exposures and multiple myeloma in Iowa men

A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR]=1.2, 95 percent confidence interval [CI]=0.8–1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD, USA. Dr Burmoistor is with the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD, USA. This project was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

多发性骨髓瘤与HBV、HCV及EBV病毒感染的关系

目的:探讨多发性骨髓瘤（multiple myeloma,MM）发病与乙肝病毒（HBV）、丙肝病毒（HCV）和EB病毒（EBV）感染之间的相关性。方法:采用多中心、以医院为基础的1∶1配对病例对照研究。265例MM病例来自西安市五家三级甲等医院血液科在2011年10月至2014年9月期间住院患者。对照来自同期、同院住院的非肿瘤患者,与病例在性别和年龄（±5岁）上匹配。ELISA方法检测研究对象血清中的HBsAg、抗-HBc、抗-HCV和抗-EBV。应用Logistic回归分析不同病毒感染与MM发病的关联性。结果:MM组HBsAg阳性率与对照组相比差异无显著性意义（7.55% vs 4.49%,P>0.05）。MM组抗-HBc阳性率明显高于对照组（45.82% vs 33.64%,P<0.01）,OR值为1.66（95%CI:1.17~2.36）。将HBsAg和抗-HBc合并分析发现两组差异有统计学意义（P<0.01）,OR值1.82（1.28~2.58）。HCV和EBV病毒阳性率在两组之间的差异无统计学意义（P>0.05）。结论:HBV感染增加MM的发病风险,而HCV和EBV感染与MM发病风险无明显关联。     

Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.     

Bortezomib,melphalan, and prednisone in elderly patients with relapsed/refractory multiple myeloma

BACKGROUND:

In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event‐free survival compared with MP alone.

METHODS:

In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose‐intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m² on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28‐day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled.

RESULTS:

After a median follow‐up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles.

CONCLUSIONS:

A weekly infusion of bortezomib associated with lower dose‐intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM. Cancer 2013. © 2012 American Cancer Society.     

Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing,proliferation, and polarization in multiple myeloma

We previously showed that macrophages (MΦs) infiltrate the bone marrow (BM) of patients with myeloma and may play a role in drug resistance. This study analyzed chemokines expressed by myeloma BM that are responsible for recruiting monocytes to the tumor bed. We found that chemokines CCL3, CCL14, and CCL2 were highly expressed by myeloma and BM cells, and the levels of CCL14 and CCL3 in myeloma BM positively correlated with the percentage of BM-infiltrating MΦs. In vitro, these chemokines were responsible for chemoattracting human monocytes to tumor sites and in vivo for MΦ infiltration into myeloma-bearing BM in the 5TGM1 mouse model. Surprisingly, we also found that these chemokines stimulated MΦ in vitro proliferation induced by myeloma cells and in vivo in a human myeloma xenograft SCID mouse model. The chemokines also activated normal MΦ polarization and differentiation into myeloma-associated MΦs. Western blot analysis revealed that these chemokines promoted growth and survival signaling in MΦs via activating the PI3K/Akt and ERK MAPK pathways and c-myc expression. Thus, this study provides novel insight into the mechanism of MΦ infiltration of BM and also potential targets for improving the efficacy of chemotherapy in myeloma.     

Association of interleukin-1A, interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms with multiple myeloma

Interleukin-1 (IL-1) is a cytokine involved in the maturation and proliferation of B cells and plays a significant role in the development of lytic bone lesions, a major clinical feature of multiple myeloma (MM) patients. Genes that regulate products involved in the immune system are highly polymorphic and contribute to inter-individual differences that can influence the genetic predisposition and progression of particular diseases and cancers. In this study, we investigated the correlation between the single nucleotide polymorphisms IL1A -889, IL1B -511, IL1B +3954, IL1RN Mspa1 +11100 and susceptibility to MM in 74 patients and 160 controls. We found that individuals possessing IL1A -889 CT polymorphism had a higher risk in developing MM. Moreover, genotypes IL1B -511 CC, IL1B +3954 CC, IL-1RN Mspa1 +11100 CC and the combination of IL 1B +3954 CC with IL1B -511 CC or IL-1RN Mspa1 +11100 CC exerted a protective effect in individuals possessing them.     

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.     

多发性骨髓瘤患者临床特征、FISH检测结果与疗效相关性的临床分析

目的:探讨初治多发性骨髓瘤（multiple myeloma,MM）患者的临床特征、FISH检测结果与不同治疗方案疗效的相关性。方法:回顾性分析54例初治多发性骨髓瘤患者临床特征、FISH检测结果、治疗方案及疗效,利用独立样本t检验比较分子遗传学与患者临床特征的关系,利用χ2检验或Fisher确切概率法比较不同治疗方案的疗效与分子遗传学异常的关系。结果:54例MM患者总有效率为61.11%（33/54）。完成FISH检测者共41例,伴分子遗传学异常者占70.73%（29/41）,其中1q21扩增、13q14缺失、p53缺失、IgH重排检出率分别为53.66%（22/41）、31.71%（13/41）、2.44%（1/41）、36.59%（15/41）,2种及以上分子遗传学异常者占48.78%（20/41）。13q14缺失阳性组患者血清校正钙水平较阴性组高（P＜0.05）,IgH重排阳性组患者骨髓浆细胞比例高于阴性组（P＜0.05）。伴有2种及以上分子遗传学异常患者总有效率及完全缓解率均低于伴有1种分子遗传学异常患者（P=0.014,P=0.005）。传统化疗组中13q14缺失、1q21扩增阳性患者总有效率均较阴性患者低（P=0.02,P=0.03）,未发现IgH重排阳性患者与阴性患者间疗效差异（P＞0.05）;硼替佐米组中基因异常患者与正常患者间总有效率相比差异无统计学意义（P＞0.05）。结论:新型治疗药物的出现使MM患者疗效得到改善,分子遗传学异常与临床特征及疗效相关,可协助判断患者预后并为治疗方案的选择提供依据,其中伴有13q14缺失阳性及1q21扩增患者治疗反应差,蛋白酶体抑制剂硼替佐米可在一定程度上改善分子遗传学阳性患者近期疗效。