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  • 1
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 14, No. 3 ( 2014-06), p. e87-e93
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
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  • 2
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    Springer Science and Business Media LLC ; 2010
    In:  Medical Oncology Vol. 27, No. S1 ( 2010-6), p. 53-61
    In: Medical Oncology, Springer Science and Business Media LLC, Vol. 27, No. S1 ( 2010-6), p. 53-61
    Type of Medium: Online Resource
    ISSN: 1357-0560 , 1559-131X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
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  • 3
    In: British Journal of Haematology, Wiley, Vol. 154, No. 1 ( 2011-07), p. 104-110
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2011
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  • 4
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2622-2622
    Abstract: Background: There is a significant variation in disease incidence and outcomes among Multiple Myeloma (MM) patients (pts) from different ethnic backgrounds. Currently, there is a paucity of data regarding the influence of demographics and ethnicity on behavioral patterns of pts, their attitudes, beliefs, and knowledge about MM and its treatment, which could in turn affect outcomes. We conducted a questionnaire-based study to examine behavioral patterns of MM pts, especially focusing on ethnic minorities and how this may impact patient awareness and symptom complex related to the disease and its treatment. Methods: Apaper-basedquestionnaire consisting of 61 questions encompassing four broad categories was provided to participating pts at the University of Southern California Medical Centers. These included demographics, disease/treatment related quality of life (QoL), satisfaction regarding treatment, and satisfaction regarding treating physician/healthcare staff. Information on clinical characteristics and MM-related treatment was collected through an IRB-approved protocol. Pts were stratified by age, gender, and ethnicity (Hispanics vs. Non-Hispanics). Any missing patient responses were withdrawn from the final analysis of that question. Categorical and continuous variables were compared among groups using Chi-square and Kruskal-Wallis tests, respectively. All statistical analysis utilized SAS software (v9.3) with a two-sided significance level of 0.05. Results: A total of 89 pts (males: 40, females: 49) from March 2012 to October 2013 responded to the questionnaire of the 100 pts that were consented (81%). Median age was 59 (range: 23-81) years and 43 (48%) pts were Hispanic while 46 (52%) were Non-Hispanic. Baseline clinical characteristics are shown in Table 1A. As compared to Non-Hispanics, Hispanic pts were less likely to have completed college (70% vs. 30%, p 〈 0.001), attend myeloma support groups (90% vs. 10%, p=0.026), feel they had sufficient disease/treatment-related information (72% vs. 22.5%, p 〈 0.001). Hispanic pts were more likely to report being unemployed/without any income (57.5% vs. 9%, p 〈 0.001), have 3-4 people living in the house (57.5% vs. 26 %, p=0.009), feeling ill (43% vs. 21%, p=0.029), have concern about deterioration in clinical condition (66% vs. 41%, p=0.022), and inability to work due to symptoms from MM or its treatment (38.6% vs. 11.9%, p=0.005) when compared to Non-Hispanics. With respect to MM treatment, Hispanic pts were less likely to report that side effects were as expected (34% vs. 57%, p=0.036) and believe that treating staff worked towards the same goal (88% vs. 100%, p=0.020) as them. Hispanic pts also reported a lower level of satisfaction with their doctor /treatment staff, as compared to Non-Hispanic pts and this difference was statistically significant as shown in Table 1B. Using gender as the stratification factor, we noted that female pts were more likely to report lack of energy (p=0.037), pain (p=0.010), satisfaction with discussion on emotional health (p=0.012) as compared to males. With age as the stratification factor, patients 〈 60 years of age were less likely to report expected effectiveness from treatment (p=0.031), satisfaction regarding appropriateness of treatment (p=0.008) or explanation of test results by their doctor (p=0.036), and were more likely to worry about deterioration in their condition (p=0.014). We did not find a statistically significant association between age, gender, or ethnicity and response to initial myeloma treatment. Conclusions: We found a significant association between MM patient ethnicity and the pts responses to questions pertaining to their QoL, satisfaction with treatment and treating physician. This difference in disease/treatment related knowledge and attitudes may be related to socio-cultural and behavioral patterns and may contribute to factors such as treatment compliance, effectiveness and symptom complex burden amongst others, that can impact outcomes among ethnic subgroups of MM pts. Efforts to mitigate these differences should focus on improving methods of patient education, spread more awareness among ethnic minorities, integration of psychosocial care into cancer therapy and promoting health psychology research. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4587-4587
    Abstract: Abstract 4587 Background: High-dose chemotherapy and autologous stem cell transplant (ASCT) remains an important therapeutic modality for MM patients. Traditionally high-dose single agent melphalan (200 mg/m2; Mel-200) has been used as the conditioning regimen prior to ASCT for MM. We investigated the combination regimen of BCNU, etoposide and melphalan (BEM) in this setting at our center. Methods: All patients who had undergone ASCT for MM utilizing BEM conditioning regimen at Norris Cancer Center, University of Southern California, Los Angeles were eligible. BEM consisted of BCNU 12 mg/kg (actual body weight or ideal body weight whichever was lower) iv on day -5, etoposide 60 mg/Kg iv on day -3, and melphalan 140 mg/m2 iv on day -1, prior to stem cell reinfusion on day 0. Overall survival (OS) was defined as time from MM diagnosis to death, or in patients still alive, the date of last follow-up. Progression-free survival (PFS) was defined as time from ASCT to date of relapse, or in patients without documented relapse, date of death or last follow up, whichever was sooner. Survival for patients with different clinical and disease-specific characteristics was explored using logrank test. Response was assessed according to International Uniform Response Criteria for MM. Results: A total of 44 MM patients underwent ASCT utilizing the BEM conditioning regimen. Of these, evaluable data was available for 42 patients (25 males; 60%, 17 females; 40%) with a median follow up of 27.6 mths. Median age at diagnosis was 54.5 yr (range 34–68) while median time from MM diagnosis to ASCT was 10.5 mths (range 2.8–47.8). MM subtypes included IgA (n=5, 12%), IgG (n=30, 71%) and light chain-only (n=7, 17%). Median bone marrow (BM) plasmacytosis at diagnosis was 42.5% (range 0%-100%). Durie-Salmon (DS) stages included stage I (12%), II (36%) and III (52%), while 4 patients (10%) had renal dysfunction at the time of initial MM diagnosis. Majority of the patients (71%) had lytic bone lesions at the time of diagnosis and 86% (n=36) hade secretory disease. Patients had received a median of 1 prior treatment (range 1–5), while 23 (55%) patients had received novel agents (proteasome inhibitors or IMiDs) prior to the BEM regimen. Response rates prior to and after the regimen are summarized in Table 1. After BEM-ASCT an additional 16 (38%) patients achieved a CR. Median duration of hospitalization and time to engraftment were 19 days (range 15–41) and 10.5 days (range 7–19), respectively. One patient died prior to discharge from the hospital post ASCT (Day 36 post ASCT) for a treatment related mortality of 2%. CR rate post BEM-ASCT was 64% with an ORR of 97%. Relapses have been noted in 25 patients to date. Median OS for all patients was 4.9 yrs (5.6 yrs for patients in CR and 6.6 yrs for patients in PR after BEM-ASCT). Median PFS was 23.9 mths for all patients (25 mths for patients in CR and 21.8 mths for those in PR after BEM-ASCT). No statistically significant differences were noted in OS based on patient gender (p=0.47), age at diagnosis ( 〈 or ≥60 yr), MM subtype (p=0.52), DS stage at diagnosis (0.09), patients without lytic bone lesions at diagnosis (p=0.054), secretor status (p=0.2), response status at the time of BEM-ASCT (p=0.9) or prior exposure to novel agents (p=0.62). Conclusions: BEM is a well-tolerated conditioning regimen prior to ASCT in MM and has efficacy comparable to Mel-200. BEM can be effectively employed in patients where Mel-200 is not feasible. We are particularly intrigued by its ability to deliver high CR rates (64%) compared to 〈 30% (historical control). Very encouraging median OS (4.9 yr) and PFS (23.9 mth) rates were noted which were even better in patients who had a measurable response after this regimen. Further investigations will be needed to optimally define its potential as standard conditioning regimen in MM patients undergoing ASCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5350-5350
    Abstract: The role of the tumor microenvironment (TME), including the heparanase/syndecan-1 (H/S1) axis in the growth and progression of multiple myeloma (MM) has been studied principally in in vitroor animal models. Targeting the TME with anti-myeloma agents such as immunomodulatory drugs (IMiDs) is considered standard but the effect of anticoagulation on the H/S1 axis has not been reported in a clinical trial setting. We investigated the combination of lenalidomide (Len; IMiD) and low-dose dexamethasone (dex) with different doses of the low-molecular-weight heparin, dalteparin (DAL), in treatment-naïve MM patients and report the effects on the H/S1 axis. Methods A randomized phase 2 clinical trial of Len+Dex with prophylactic (5000IU) or therapeutic (200IU/Kg) doses of DAL in newly diagnosed MM patients was initiated. Patients were administered 14 days of respective DAL dose alone as a “run-in” and then Len+Dex were added for a maximum of 6, 28-day cycles. Peripheral blood collection was done on day (D)-14, D-7, D1, D7, D15 in cycle1 and then D1 of each subsequent cycle to measure D-dimer, Syndecan-1 and IL6 levels by ELISA. Log-transformed levels were used in a linear model to test for differences between the two doses of DAL overall, changes over time, as well as different change patterns between the two doses. Basic summary statistics and scatterplots were used to summarize the data, while untransformed data were used for non-parametric summary numbers (medians, ranges, Spearman correlation). Means and associated 95% confidence intervals (CI) were based on the log-transformed values and anti-log transformation was used to present the results in the original scale, with the result that differences between the two groups were reported as ratios. Results Eleven patients (5 females, 6 males) have been enrolled in the ongoing trial (target accrual: 30), of which one was ineligible due to an acquired factor VIII inhibitor. Median age at study onset was 60.8 years (range 38.1-69.9 years). Disease stage included International Staging System (ISS) I in 5, II in 4 and III in 2 patients. Lytic lesions at diagnosis were present in 6 (55%) patients while plasmacytomas were noted in 5 (45%) patients. Median bone marrow plasmacytosis was 40% (range 10%-90%). One case of venous thrombosis was noted on treatment in the high-dose arm after 4 cycles of treatment. We did not find any correlations between baseline levels of D-dimer, IL6 or Syndecan with patient age, gender, ISS stage, presence of lytic lesions or plasmacytomas. No significant correlation was observed between the changes in these three parameters over time or related to DAL dose. However, observing shorter treatment periods showed that the D-dimer decreased significantly between C1D-14 and C1D1 for the low-dose group (mean 0.52; 95% CI 0.37, 0.72), high-dose group (mean 0.44; 95% CI 0.31, 0.65) and all patients taken together (mean 0.48; 95% CI 0.4, 0.59). We also noted a significant increase in Syndecan-1 between C1D-14 and C1D1 for the high-dose group (mean 2.06; 95% CI 1.3, 3.25) and for all patients taken together (mean 1.71; 95% CI 1.28, 2.27), but not for the low-dose group. No significant change was noted in IL6 for this period. However, a significant increase in IL6 was noted early on after the introduction of Len+Dex to DAL between C1D1 and C1D15 in the high-dose (mean 3.21; 95% CI 1.17, 8.8) and overall (mean 2.46; 95% CI 1.52, 3.99) patient groups. These changes did not persist in subsequent treatment periods. Conclusions In an ongoing phase 2 clinical trial focused on the modulation of H/S1 axis in response to treatment of MM with IMiDs and DAL, we noted a significant decrease in D-dimer when patients were treated with DAL alone prior to initiating Len+Dex. We observed a significant increase in Syndecan-1 in all patients as well as in the high-dose group in response to treatment with DAL alone. We also noted an IL6 flair phenomenon, with a significant increase in IL6 in all patients immediately after the initiation of Len+Dex. These initial findings suggest significant modulation of the MM microenvironment by LMWH. Disclosures: Off Label Use: Use of lenalidomide for treatment-naive multiple myeloma patients, Use of dalteparin for prophylaxis of thromboembolism in multiple myeloma patients treated with immunomodulatory agent with dexamethasone. O'Connell:Celgene Corp.: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 728-728
    Abstract: Abstract 728 Background: LM, an antibody-drug conjugate (ADC), is designed to specifically kill CD56+ cancer cells and contains a potent maytansinoid cytotoxic agent (DM1) attached to a CD56-targeting antibody. MM shows CD56 expression in 〉 70% of cases. LM has demonstrated single agent clinical activity and an acceptable safety profile in relapsed/refractory (rel/ref) MM patients. Preclinical studies showed enhanced anti-MM activity when LM was combined with Len/Dex. To further study the safety and efficacy of LM in combination with Len/Dex, a phase I study was conducted in rel/ref patients. This abstract reports updated results on the safety and efficacy of LM/Len/Dex and preliminary results on the pharmacokinetics (PK) and immunogenicity studies. Methods: Primary study objectives were to determine the safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), anti-MM activity and PK of LM in combination with standard oral (PO) doses of Len (25 mg po, daily on days 1–21) and Dex (40 mg po on D 1, 8, 15, and 22) in CD56+ rel/ref MM patients who have received at least 1 prior therapy. LM was given intravenously (IV) on D 1, 8, and 15 on a 28-day cycle. Dose escalation was conducted in new cohorts of patients to define the MTD, which was then further evaluated in a dose-expansion cohort. Adverse events (AEs) were assessed using CTCAEv3 criteria, and dose-limiting toxicity (DLT) determination was based on the occurrence of AEs that were probably or definitely attributed to the study regimen. Efficacy was assessed using the International Myeloma Working Group (IMWG) criteria. Enrollment has completed and 16 patients remain on study. Results: Forty-four patients were enrolled, 41 are currently evaluable for safety and 32 are evaluable for efficacy. The median number of prior therapies was 2 (range 1–11), 62% of patients had prior Len exposure and 33% were Len refractory. LM doses of 75 (N = 11), 90 (N=4), and 112 (N =6) mg/m2 were evaluated in the dose-escalation phase. The most common AE was peripheral neuropathy (PN), which occurred more frequently at higher LM doses (55% at 75 mg/m2 and 100% at 90 and 112 mg/m2); Grade 3 PN was seen only in patients treated at 90 mg/m2 or above. PN emerged, in most cases, in cycles 〉 3 and was manageable with LM dose modification. During dose escalation, 1 patient experienced Grade 4 neutropenia and hyperuricemia. The 75 mg/m2 LM dose was considered the MTD based on overall tolerability and the lower incidence of PN observed, and was further tested to determine its suitability as the RP2D in the dose expansion portion of the study (N=23 patients, 19 patients available for safety evaluation). Grade 1–2 PN occurred in 8 patients (42%) and grade 3 PN was observed only in 1 pt in the dose-expansion cohort. Two patients developed grade 3 tumor lysis syndrome (TLS). Other grade 3 AEs reported in 1 patient each (5%) in the dose-expansion cohort consisted of neutropenia, thrombocytopenia, anemia, hemolytic anemia, and LDH increase. Efficacy was observed across all dose levels and the overall response rate (ORR) was 59%, including 1 patient each with stringent complete response (sCR) and complete response (CR), 8 patients with very good partial remission (VGPR), and 9 patients with partial remission (PR). No immunogenicity against the antibody (HAHA) or DM1 component (HADA) of LM was detected. PK results from 18 patients treated at 75 mg/m2 indicate LM Cmax and exposure in this combination regimen is consistent with LM monotherapy. Conclusions: Based on all available safety data, 75 mg/m2 was considered the RP2D. LM at 75mg/m2 in combination with Len and Dex has shown objective evidence of clinical activity with an acceptable safety profile. Disclosures: Off Label Use: Lorvotusumab mertansine is not FDA approved for treatment of multiple myeloma alone or in combination with lenalidomide and dexamethasone as is investigated in this trial. Running:ImmunoGen, Inc.: Employment. Murphy:ImmunoGen, Inc.: Employment. Guild:ImmunoGen, Inc.: Employment. Carrigan:ImmunoGen, Inc: Employment. Ladd:ImmunoGen, Inc.: Employment. Wolf:ImmunoGen, Inc.: Employment, Equity Ownership. O'Leary:ImmunoGen, Inc.: Employment. Ailawadhi:Millenium Pharmaceuticals: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 8
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1294-1294
    Abstract: Background: Outcomes in multiple myeloma (MM) have significantly improved, leading to higher prevalence of this disease. Increasing efforts have been made by various agencies to educate patients (pts), manage quality of life (QoL) and survivorship. A global impact of these efforts including pt awareness, disease knowledge and participation in their care, as well as the physical and emotional impact of MM and its treatments (Rx) has not been assessed. We undertook an international, pt-reported survey to investigate these factors and understand any underlying disparities. Methods: A 61-question patient-reported questionnaire (MM-Q), addressing global aspects of MM pts care (components in Figure 1) was used. MM-Q was administered in collaboration with the International Myeloma Foundation (IMF). To limit responses by MM pt only, SmartPatient MM community members and IMF Support Group Leader list were invited to complete the survey. Some of the questions were mandatory, and those with missing responses were withdrawn from the final analysis of that pts MM-Q. Categorical and continuous variables were compared among groups using the Chi-square and Kruskal-Wallis tests, respectively using SAS software (v9.3) with a two-sided significance level of 0.05. Results: Survey responses are available from 894/1240 (72%) individuals thus far. Average survey completion time was 16 minutes. Data from 746 MM-Q was included in this analysis with 466 (62.5%) complete responses. Pts from United States (US) represented 85.7% of the responders (majority from New York State). Ethnicity (n=590) was reported as non-Latino by 97%, race (n=580) was reported as White by 95%, family history of MM was reported by 19 pts and 81 reported prior history of a primary malignancy (most common, 37% non-melanoma skin cancer). Living situation questions (n=538) revealed majority were in a household of 2 (62%), were unemployed/on public assistance (53.5%), travelled alone to medical appointments (74%), with travel times varying from 〈 30 min (55%) to 〉 1 hr (17%). Majority (83%) had no prior knowledge of MM, 63% were patient support group members, and 92% did MM-related research on internet. With respect to MM Rx (n=524), 70% had been on Rx within 3 months and 12% reported non-compliance. Prior Rx included thalidomide (30%), lenalidomide (66%), pomalidomide (11.5%), bortezomib (63.5%), carfilzomib (11%), steroids (100%), and clinical trial participation in 25% pts. Side effects from Rx/QoL in prior 3 months (n=403) are summarized in figure 2. Pts satisfaction with Rx/treating staff (n=378) revealed majority felt their Rx to be effective (92%), right for them (87%) and side effects were as expected (84%). In general, pts acknowledged positive attributes of the Rx staff (worked towards same goal; 91%, participated in decisions; 81%, honesty 89%, confidence; 92%), and their doctor's explanations regarding Rx (benefits; 84%, side effects; 74%, test results; 83%), with the exception of emotional effects of Rx (48%). 94% pts rated their care as good/excellent and 95% were willing to participate in a follow-up survey. Stratification of statistically significant responses by geographical categories, age and time since diagnosis are shown in table 1 and analysis by occupation and educational status is ongoing. Conclusions: We conducted a large patient-reported survey to understand the current state of awareness among MM pts and a global impact of the diagnosis and its Rx on them. We showed that majority of pts who accessed the survey responded (72%), which may be a product of literacy, education and access to technology. Majority of the pts were White and non-Latino, highlighting the possible role of access and awareness in ethnic minorities. We report the large prevalence of psychophysical burden of MM and its Rx in MM pts. In general, MM pts had a high rate of satisfaction related to the Rx and their healthcare providers, but the frequency of discussion regarding emotional effects of Rx between doctors and pts was conspicuously low (48%) and the more recently diagnosed pts were less likely to be satisfied with their treating staff. We also demonstrated significant behavioral pattern differences in geographical, age and time-since-diagnosis subgroups, some of which may be sociocultural, while others may be a result of more patient awareness and understanding of the disease. This knowledge will be very helpful in devising MM survivorship strategies. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 9
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2030-2030
    Abstract: Multiple myeloma (MM) is 2-3 times more common among African-Americans compared to non-Hispanic whites. The 2-3-fold increased risk among family members of cases suggests a genetic contribution to risk. Genome-wide association studies (GWAS) in populations of European ancestry have identified seven novel risk loci at 2p23.3 (rs6746082), 3q26.2 (rs10936599), 3p22.1 (rs1052501), 6p21.32 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077) and 22q13.1 (rs877529) (Broderick, et al. Nat Genet, 2011, Chubb, et al. Nat Genet, 2013), three of which were replicated in another European series (Martino et al., Br J Haematol, 2012). Here we examined the index signals and conducted fine-mapping for each locus in a case-control study of 1,049 multiple myeloma cases and 7,084 controls of African ancestry to identify better markers of risk and novel independent loci in seven previously reported regions in this high risk population. Incident cases were recruited from 10 clinical centers and SEER cancer registries from 2011 to 2013 and genotyped using the Illumina HumanCore GWAS array. Control data were obtained from previous genome-wide studies of breast and prostate cancer, genotyped using the Illumina 1M-Duo in 4425 male controls from the African Ancestry Prostate Cancer Consortium (consisting of 14 independent studies) and 2632 female controls from a breast cancer GWAS of African-American women (consisting of 9 independent studies). Imputation to 1000 Genomes (March 2012 release) was conducted for regions around six of the previously identified single nucleotide polymorphisms [SNPs] (the HLA region harboring rs2285803 is still being imputed, results will be presented). A case-control analysis of SNPs/indels 〉 1% frequency within 250 kb of each index variant was conducted using unconditional multivariable logistic regression adjusting for age, sex and five leading principal components. Region-specific alpha levels were determined through permutation tests. The minimum alpha level across the six regions was α=0.002. All previously reported risk variants were common in African-Americans (minor allele frequency [MAF] 〉 0.05). For five of the six SNPs, we had ≥94% power to detect the same effect observed in non-Hispanic whites, and 64% power for the less common variant rs10936599 (MAF=0.07). We observed directionally consistent effects (odds ratio [OR] 〉 1) for the six risk variants tested, with three replicating at p≤0.05 (7p15.3, p=1.4x10-7; 17p11.2, p=0.05; 22q13.1, p=0.02). For three of the six regions, we observed better markers of risk in African-Americans that were correlated with the index SNP in Europeans (7p15.3, rs56333627, p=1.5x10-5, r2=0.89; 17p11.2, rs34562254, p=2.9x10-3, r2=0.90; 22q13.1, rs2092410, p=1.1x10-4 r2=.71). The missense variant identified in the 17p11.2 region (rs34562254, Pro251Leu) is located in TNFRSF13B, which encodes the protein TACI, a B cell surface receptor which plays a role in B cell maturation, apoptosis and antibody production by inducing activation of transcription factors including NFAT and NFκβ. In addition, there is evidence suggesting that TACI is involved in MM pathogenesis. Our results demonstrate that many of the risk loci for MM found in European ancestry populations are also risk loci in men and women of African ancestry and that by fine-mapping, we are able to identify variants that better capture risk in populations of African ancestry. Disclosures Terebelo: Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 10
    Online Resource
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    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 3958-3958
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3958-3958
    Abstract: Abstract 3958 Introduction: Recent advances in the treatment of multiple myeloma (MM) have lead to improved patient outcomes and significant improvement in MM survival. Reports from ongoing randomized clinical trials have suggested that there may be an association between the types of treatment received, particularly certain novel therapeutic agents, and a higher incidence of second primary malignancies (SPM) among MM patients. In this analysis, we explored current patterns and trends in incidence and survival of MM between 1973–2008 to better characterize MM patients with second primary malignancies. Methods: We used data from the National Cancer Institute Surveillance Epidemiology and End Results Program (SEER) to examine the incidence and survival trends in MM by SPM status between 1973–2008. We included all cases with MM as the first primary malignancy and calculated the age-adjusted annual incidence rates (AIR per 100,000) stratified by those with single primary (SP) MM and those with MM as the first of multiple primaries (FMP). All cases that were not microscopically confirmed or those with an MM diagnosis coded only from autopsy- or death certificates were excluded from the analysis. We used joinpoint regression models to calculate the annual percent change (APC) and to determine the best fitting line or set of lines that describes the MM temporal trends. A Monte Carlo permutation method was used to test for significance. We used multivariate Cox proportional hazard models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for MM by SPM status, and all analyses were further stratified by year of diagnosis, age, sex, and race/ethnicity. Results: A total of 61,411 cases of MM were recorded in all SEER registries between the years 1973 and 2008. The final analysis included 49,801 SP and 3090 FMP cases. Overall, the AIR of MM was 5.31 (95% CI 5.26–5.36). The AIR of SP MM was 4.33 (95% CI 4.28–4.38) and 0.28 (95% CI 0.27–0.29) for FMP MM. Compared to women, men were 1.41 times (95% CI 1.38–1.44) and 1.95 times as likely to develop SP MM and FMP MM, respectively. African-Americans had the highest rate of SP MM (AIR 9.09; 95% CI 8.85–9.34) and FMP MM (AIR 0.69; 95% CI 0.62–0.76). We observed no significant trend in AIR of SP MM between 1973–2008 (APC 0.03). The rate of FMP MM was relatively stable, however we observed a small but statistically significant increasing trend in incidence between 1973 and 1992 (APC 2.9), followed by a decreasing trend between 1992 and 2008 (APC −3.2). The rate ratio of FMP to SP MM has remained stable at approximately 6% from 1973–2008. The overall hazard ratio of mortality was 0.59 (95% CI 0.56–0.61) with a median survival of 3.6 years in the FMP MM versus 1.7 years in the SP MM patients. There was a statistically significant improvement in the survival of SP MM patients over the past three decades (P for trend 〈 0.001), with the most prominent increase in the 2002–2008 period with a HR of 0.67 (95% CI 0.64–0.69) when compared to those diagnosed in the 1973–1981 period. In contrast, the survival of FMP MM patients remained constant (P for trend=0.39). Although SP MM patients show a significant increase in survival over time, FMP MM survival remained stable and significantly higher. We further stratified the survival analysis by age, sex, and race/ethnicity. In all stratified analyses, FMP MM patients had a significantly better outcome compared to SP MM patients. Conclusions: Although there has been significant improvement in survival for patients with SP MM in recent years, our results provide an epidemiologic evidence suggestive of a subtype of MM with a better outcome, yet a higher risk of secondary primary malignancies. The incidence rate and outcome of this possible subtype has remained unchanged over the last three decades. These findings are replicated when stratified by gender, race, age, and year of diagnosis. Recent advancements of MM treatment have seemed to only increase the survival of SP MM patients, while the survival of FMP MM patients remained stable. Further studies are needed to explore the potential genetic heterogeneity between MM with and without second primary malignancies. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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