Explaining the Excess Risk of Multiple Myeloma in African-Americans

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4002-4002 ◽  
Author(s):  
Wendy Cozen ◽  
Amie E. Hwang ◽  
Sikander Ailawadhi ◽  
Seema Singhal ◽  
Carol Ann Huff ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Predominantly White ◽  
Hodgkin Lymphoma ◽  
Light Chain ◽  
Cancer Registries ◽  
Population Based ◽  
Bone Lesions ◽  
Lytic Bone Lesions

Abstract Abstract 4002 African-Americans (AA) have a 2–3-fold higher risk of multiple myeloma (MM) relative to Whites (Gebregziabher, 2006). We have formed a consortium and are conducting a multi-center study with 9 clinical centers and 4 NCI Surveillance, Epidemiology and End-Results (SEER) Program population-based cancer registries to determine the causes of the disease in this population and explain the excess risk (Myeloma in African-American Patients, MAP). Participation involves providing a blood or saliva specimen for DNA and answering a lifestyle and medical history questionnaire. At the end of the data collection period, a genome-wide scan will be performed and our results compared to those from 2,000 African-American controls participating in cohort studies. Patients with African ancestry (predominantly African-Americans) are identified from outpatient clinic rosters or from population-based cancer registries. For patients recruited at clinics, information on subtype, cytogenetics, FISH and lytic bone lesions is abstracted from medical records. To date, 601 patients have agreed to be in the study and we have received DNA samples from 592 patients; 54.6% are female and 45.4% are male. The mean age at diagnosis is 57 years (SD =11.2) with a median age at diagnosis of 58 years (range 27 to 90 years of age). Of the 514 subjects who completed a questionnaire, 7.8% were obese at age 20 (body mass index > 30) and 39% were obese 5 years prior to diagnosis. A first-degree relative with MM was reported by 17 cases (3%), 74% higher than the lifetime risk of 1.7% in the general population based on SEER data. In addition, cases reported 21 first-degree relatives with leukemia (4%), 7 with non-Hodgkin lymphoma (1%) and 14 with Hodgkin lymphoma (3%). To date, clinical information has been abstracted for 351 patients. Of these, 207 (58%) have active disease with the following distribution: stage I (30%), stage II (27%) and stage III (43%). The remainder have relapsed (13%), refractory (1%), relapsed and refractory (4%), or smoldering myeloma (6%), or are in remission (18%). The subtype distribution is: IgG (74%), IgA (11.4%), IgD (0.9%) and IgM (0.3%), and light chain only (13.5%); a distribution significantly different from that observed in a predominantly White population (P <0.007) (Kyle, 2003), (Table 1). Lytic bone lesions were present in 67% of patients, similar to the prevalence observed in other series. FISH and cytogenetics data on hyperdiploidy, deletions in chromosome 13 and 17p, and IGH translocations are being collected on this large cohort of African-Americans patients and will be presented at the ASH meeting. Disease characteristics in AA patients appear to be different than those previously reported in predominantly White populations. Table 1. Type of multiple myeloma and presence of bony lesions in 351 African-American patients. African-American Patients Mayo Clinic1 n % % Type     IgA 38 11.4 20     IgD 3 0.9 <10     IgG 247 74 50     IgM 1 0.3 <10     Light Chain only 45 13.5 20     Total 334     Not Available 17 Lytic Bone Lesions     Present 160 67 70     Absent 79 33     Total 239     Not Available 112 1 Kyle RA, Gertz MA, Witzig TE, Lutz JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Themeau TM, Gregg PR, Review of 1,027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc, 78: 21–33, 2003. Disclosures: No relevant conflicts of interest to declare.

African-American Multiple Myeloma Patients Have a Better Survival Than Caucasian Patients: a Population-Based Study Including 28,636 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1832-1832 ◽  
Author(s):  
Ola Landgren ◽  
Susan Devesa ◽  
Pamela Mink ◽  
William F Anderson ◽  
Brendan Weiss ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Excess Mortality ◽  
Survival Rates ◽  
Population Based ◽  
Age Group ◽  
Population Based Study ◽  
Caucasian Patients ◽  
Survival Patterns

Abstract Abstract 1832 Poster Board I-858 Background Multiple myeloma is the most common hematologic malignancy in African-Americans with twice the incidence of Caucasians. Prior single center studies have reported poorer survival among African-American multiple myeloma patients. In contrast, recent data based on multiple myeloma patients who received autologous transplantation in an equal access health care system, showed comparable survival between African-Americans and Caucasians, suggesting that the reportedly poorer outcome for African-Americans may be due to inequalities in access to care. Also, based on publicly available cancer registry data, several publications have reported excess mortality rates for African-American multiple myeloma patients. We conducted a large population-based study including almost 30,000 multiple myeloma patients to evaluate survival patterns by race. Methods. Patient information was obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registries of the National Cancer Institute. Data were drawn from the original nine SEER registries (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, and Utah), which collectively cover approximately 10% of the U.S. population. Using the SEER*Stat statistical software package, we calculated 1-, 5-, and 10-year relative survival rates (RSR) of multiple myeloma patients diagnosed 1973-2004. We applied four calendar periods (1973-1979, 1980-1986, 1987-1993, and 1994-2004), follow-up through 2005 was included, and age at diagnosis was grouped into three strata (<50, 50-64, and 65+ years). Results We identified a total of 28,636 multiple myeloma patients (4,855 African-American; 23,781 Caucasian); 64% were 65 years or greater at diagnosis. When we included all patients, a comparison of survival rates in African-American and Caucasian males showed that African-American males had significantly better 5-year (32.2% vs. 28.7%) and 10-year (16.4% vs. 11.5%) RSRs (p<0.05). Similarly, African-American females had significantly better 1-year (73.3% vs. 70.2%) and 5-year (31.1% vs. 27.7%) RSRs than Caucasian females (p<0.05). When we examined survival patterns by calendar period (between 1973-1979 and 1994-2004), we found Caucasian patients to have significant improvements in the 1-year (from 67.1 to 72.4%), 5-year (from 24.1% to 31.7%), and 10-year RSR (from 9.9% to 14.9%). African-Americans also showed significantly improved 1-year RSRs (from 68.5% in 1973-1979 to 74.9% in 1994-2004) but the improvements in 5- and 10-year RSRs were not significant. When we examined survival patterns by age group, in the youngest age group (<50 years), both African-Americans and Caucasians improved 5- and 10-year RSRs, while 1-year RSR was improved for Caucasians only (from 80.9% to 84.9%). For patients 50-64 years, Caucasians had significantly improved 1-, 5-, and 10-year RSR; for African-Americans only 1-year RSR improvement was significant. Among patients 65+, there was no significant improved survival for African-Americans while Caucasians had improved 1-year (from 61.4% to 66.9%) and 5-year (from 19.6% to 24.7%) RSRs. Conclusions This large study of almost 30,000 patients found African-American multiple myeloma patients to have a significantly better prognosis than Caucasian patients, suggesting there is disease heterogeneity by race. After the introduction of newer therapies (autologous transplant, IMiDs, and bortezomib), Caucasian multiple myeloma patients showed a more pronounced survival benefit which might reflect inequalities in access to modern care; however, still African-Americans showed similar/better survival compared to Caucasians. Clinicians should be aware that the excess mortality rates for multiple myeloma among African-Americans, to a major degree, is a reflection of the fact that multiple myeloma is 2- to 3-fold more common among African-Americans. Future studies are needed to improve our understanding of the molecular basis for racial disparity patterns in multiple myeloma. Ultimately, such efforts will facilitate an improved understanding regarding disease subtype-specific benefits for individual agents, as well as mechanistic insights into drug sensitivity and resistance. Disclosures Weiss: The Binding Site, Inc.: Research Funding.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

Abstract 15312: Racial Disparities in Trends in Mortality From Cardiac Arrests in the United States

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anas M Al Zubaidi ◽  
Graham Bevan ◽  
Mariam Rana ◽  
Abdul Rahman Al Armashi ◽  
Mustafa Alqaysi ◽  
...  
Keyword(s):  
United States ◽  
Cardiac Arrest ◽  
African American ◽  
African Americans ◽  
Cause Of Death ◽  
Census Data ◽  
International Classification Of Diseases ◽  
The United States ◽  
Population Based ◽  
Increased Risk

Background: African Americans are at increased risk of fatal cardiac arrests, but population-based studies exploring contemporary epidemiology are not available. We sought to identify the trend in race-specific mortality from cardiac arrest in the United States. Methods: Using the multiple cause of death database, we identified all patients (Caucasians or African Americans) who died of cardiac arrest (International Classification of Diseases, 10th revision code I46.x listed as underlying cause of death) between 1999 and 2018. Age-adjusted mortality rates were standardized to the 2000 US census data, and stratified by age group (<35 years, 35-64 years, and ≥ 65 years). Results: A total of 311,065 cardiac arrest deaths were identified, with an overall age-adjusted mortality of 53.6 per million (Caucasian: 49.1 per million, African American: 90.6 per million). Overall, age-adjusted mortality decreased from 80.1 per million persons (1999) to 44.3 per million persons (2012), followed by 8.8% increase to 48.2 (2018). Between 2012 and 2018, African Americans had higher rates of increase (10.9%) compared with Caucasians (6.9%). Largest disparities in relative changes between 2012 and 2018 occurred in patients younger than 35 years (African American: 35%, Caucasians -11%), and patients ≥ 65 years (African Americans: 8%, Caucasians 4%), figure. Conclusions: Although the mortality due to cardiac arrest has declined in the US between 1999 and 2012, a recent increase has been noted between 2012 and 2018, particularly among younger African Americans. Studies should focus on identifying causes of disparities and identifying methods to reduce the racial gap.

scholarly journals Dual light chain extramedullary myeloma presenting with mediastinal lymphadenopathy and lytic bone lesions

2016 ◽  
Vol 9 (4) ◽  
pp. 162-164
Author(s):  
Panagiotis J. Vlachostergios ◽  
Katerina G. Oikonomou ◽  
Adnan Hussain ◽  
Rakesh Abbi ◽  
Rajeev L. Balmiki
Keyword(s):  
Light Chain ◽  
Mediastinal Lymphadenopathy ◽  
Bone Lesions ◽  
Lytic Bone Lesions

Seeking Diagnostic Confidence in Typing Amyloidosis: Prospective Results with an Algorithm To Minimize Misdiagnosis of Immunoglobulin Light-Chain (AL) Amyloidosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5099-5099
Author(s):  
Raymond L. Comenzo ◽  
Ping Zhou ◽  
Limin Wang ◽  
Bradly D. Clark ◽  
Martin Fleisher ◽  
...  
Keyword(s):  
African American ◽  
Peripheral Neuropathy ◽  
African Americans ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cardiac Amyloid ◽  
Hereditary Amyloidosis ◽  
The Usa

Abstract In order to treat patients with symptomatic amyloidosis, the amyloidosis must be typed with confidence. Immunohistochemical techniques for light-chain isotype identification of amyloid are not reliable, and techniques to type fibrils extracted from clinical specimens are neither widely available nor validated. Retrospectively, investigators in the United Kingdom have shown that hereditary amyloidosis can be misdiagnosed as AL in 10% of cases because family history is often not relevant and because a monoclonal gammopathy (MG) and an hereditary variant can be present in the same patient (NEJM2002;346). The most common types of amyloidosis in the USA are AL and hereditary, the latter due to mutations in proteins such as transthyretin (TTR), fibrinogen A α-chain (FnAα), apolipoprotein AI or AII, and lysozyme. The genes for these proteins are not routinely examined in all cases of likely AL amyloidosis, and clinical genetics laboratories do not offer screening for all of them. The most common hereditary variant in the USA is the V122I transthyretin mutation found in 4% of African-Americans. In addition, a common presentation of both AL and hereditary amyloidosis is peripheral neuropathy. Furthermore, in the case of FnAα nephropathy, patients usually have isolated renal amyloid without marrow involvement. To minimize the risk of misdiagnosis of AL at our center, we prospectively tested four categories of patients with a tissue diagnosis of amyloidosis for hereditary variants whether or not MG was present: African-Americans, patients with dominant peripheral neuropathy (PN), patients with isolated renal amyloidosis (RA) without marrow involvement, and patients referred for hereditary testing or lack of MG. Testing was by PCR amplification and sequencing of genomic DNA. From 6/1/02 to 8/1/05, we evaluated 178 patients referred for amyloidosis, and 30% (n=54) were screened according to this algorithm: 20 African-Americans (16 with MG), 16 with PN (11 with MG), 7 with RA without marrow amyloid (all with MG), 7 referred for hereditary testing and 4 without MG. Of those with amyloidosis and monoclonal gammopathies, 6% (2/34) had both a monoclonal gammopathy and heterozygosity for a mutant TTR: a 45 year-old African-American man (V122I) with cardiac amyloid and a 59 year-old man (F64L) with polyneuropathy. Of the 9 African-American and PN patients without MG, 4 had mutant TTR. Of 7 sent for hereditary testing, 6 had mutant TTR, one of whom also was found to have undiagnosed stage I lambda light-chain myeloma. Of 4 without MG, 2 had senile cardiac amyloid, 1 AA and 1 had amyloid that could not be typed. For those with mutant TTR and MG, TTR tissue-staining resolved the type of amyloid. These results justify further study of screening for hereditary variants in patients with apparent AL, including those with AL associated with multiple myeloma. Myelotoxic therapies such as stem cell transplant are not appropriate treatments for patients with hereditary amyloidosis. These results also highlight the need for the development, validation and dissemination of reliable techniques for identifying fibrils extracted from tissue, and raise the question as to whether or not hereditary amyloid proteins increase the risk of developing MG.

Pegylated Liposomal Doxorubicin (PLD), Vincristine and Reduced-Dose Dexamethasone (DVd) in the Treatment of Predominantly African American Population with Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5105-5105 ◽  
Author(s):  
Anshul Bamrolia ◽  
Ahmad Jajeh ◽  
R. Catchatourian ◽  
David Osafo ◽  
Deimante Tamkus ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Liposomal Doxorubicin ◽  
Mononuclear Phagocytes ◽  
Disease Stage ◽  
Phospholipid Vesicle ◽  
American Population ◽  
African American Population

Abstract Biologic therapy is emerging as first line therapy for multiple myeloma. However, most patients will require multiple lines of treatments and chemotherapy remains a very good option. In the last few years, there has been an important recognition of potentially different responses to pharmaceuticals based on genetic predisposition, starting with the FDA advisory panel recommending approval of a heart failure drug for African Americans. Liposomal doxorubicin (DOXIL; PLD) is a microscopic pegylated phospholipid vesicle with a core containing conventional doxorubicin. The pegylated coat protects the liposomes from detection by mononuclear phagocytes, increasing blood circulation time (t1/2=55 hours). Due to its prolonged half life, PLD provides a similar effect to using continuous infusion doxorubicin, but administered over 1-hour, transforming the regimen into an outpatient treatment. PLD has also been shown to have a significantly better safety profile than conventional doxorubicin. We evaluated the efficacy and safety of DVd in a predominantly African American population. A phase II trial using DVd was started in October 2000(PLD 40 mg/m2, vincristine 2 mg IVP and dexamethasone 40 mg PO 1-4 d every 4-weeks). Thirty-four patients have received DVd (15 males/19 females: mean age 59 years [range 42–77]) (five patients were off-study but received DVd per protocol). The majority of patients are African American (70%), a patient population not commonly studied. Patients presented with relatively advanced disease (stage II–III). Baseline mean serum albumin level was 3.5 mg/dl (range 1.8 to 4.9), beta-2 microglobulin 4.09 (range 1.0–8.97). Seventeen patients had IgG Kappa, seven patients had IgG lambda, six patients had IgA and four patients had light chain disease. Twenty five patients completed six cycles of therapy, with two patients completing five cycles. Six patients underwent autologous bone marrow transplant following their response to DVd. Response was assessed on the basis of a reduction of the paraprotein in serum or urine that lasted for at least six weeks. A response was achieved in 27 patients of whom 15 had a CR or nCR. 2 patients had stable disease, and disease progressed in four patients based on Blade Response Assessment. One patient died before response could be assessed. Median follow up is 36 months (range 3 months to 5 years). Our median time to progression is approximately 1 year. Twenty four patients are still alive, one patient has been lost to follow up and nine deaths have occurred. Four early deaths were due to disease progression and sepsis. Three of the early deaths had amyloidosis. Two died after one year of therapy due to progressive refractory disease. One died after the second cycle because of sudden cardiac death with sepsis. No episodes of cardiac dysfunction were observed. For African Americans, who have a high incidence of hypertension, renal and cardiovascular disease, a cardiac safer liposomal doxorubicin may be the preferred form of anthracyline.

Epidemiology and Clinical Outcomes of the M-Component Immunoglobulin Types of Multiple Myeloma in an Inner City Hispanic Population.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4736-4736
Author(s):  
George Nicolas Batty ◽  
Jonathan Brower ◽  
Adel Aziz ◽  
Neelima Maddukuri ◽  
James Tadros ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African Americans ◽  
Inner City ◽  
Clinical Outcomes ◽  
Ethnic Groups ◽  
Light Chain ◽  
Chi Square ◽  
Chi Square Test ◽  
Related Mortality ◽  
New Onset

Abstract Introduction: Different types of myeloma are classified by the type of immunoglobulin. From prior analysis, we know that IgG is the commonest class of myeloma and that this type seems to be the most benign. While IgA myeloma appear to be of intermediate outcome, IgD myeloma and lambda light-chain disease are the most aggressive types. Breakdown by immunoglobulin type reveals higher prevalence of IgG myeloma among Whites, compared to Blacks. This study examines the type of immunoglobulin and clinical implication in Hispanics compared to other ethnic groups. Methods: In a single inner city institution, we retrospectively examined patients diagnosed with multiple myeloma over a 5-year period. This investigation defined Hispanic patients as those of Latin American descent. We identified the M-component immunoglobulin type from immunoelectrophoresis as reported in medical records. New onset renal failure and disease related mortality are considered as adverse clinical outcomes. Various ethnic groups were compared between the type of immunoglobulin and adverse clinical outcomes using chi-square test. Results: A total of 203 patients were examined, of which 63 (30.9%) were Hispanics, 87 (42.9%) Caucasians and 53 (26.2%) African American, (104 males, 99 females, age range 34 – 93 yrs, mean age 67.45 ± sd 10.28 yrs). IgG and IgA M-components predominated among all ethnic groups respectively Hispanics 36 (57.9%), 6 (10.5%), Caucasians 51 (59%), 18 (22.7%) and African Americans 25 (50%), 20 (37.5%). A higher proportion of light-chain cases were seen among Hispanics since 21 (31.6%) had no peak on immunoelectrophoresis compared to Caucasians 31 (18.3%) and African Americans 8 (12.5%) (chi-square test, two-tailed p=0.426). Adverse clinical outcomes of new onset renal failure developed correspondingly in 20 (31.6%) Hispanics, 31 (36.3%) Caucasians and 15 (28.6%) African Americans while disease related mortality occurred in 20 (31.6%) Hispanics, 18 (21.4%) Caucasians and 9 (18.2%) African Americans (chi-square test, two-tailed p= 0.132). However, differences were not statistically significant. Conclusion: Although Hispanics exhibited more myeloma of light chain type and worse clinical outcomes compared to other ethnic groups, our study was unable to detect a statistical disparity. Further prospective large population based studies via the new light chain immunodiagnostic assay are warranted to define the epidemiology of this disease.

Obesity is Associated with a 2-Fold Elevated Risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) Among African-American and Caucasian Women.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4876-4876
Author(s):  
Ola Landgren ◽  
Vincent Rajkumar ◽  
Ruth Pfeiffer ◽  
Robert Kyle ◽  
Jerry Katzmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
African Americans ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Pearson Correlation ◽  
Elevated Risk ◽  
Caucasian Women ◽  
Undetermined Significance

Abstract Abstract 4876 Background Recent studies have found obesity to be associated with a 1.5- to 2-fold elevated risk of developing multiple myeloma. This is of particular interest given that elevated levels of the pro-inflammatory cytokine interleukin (IL)-6 have been found in obese persons, and, at the same time, IL-6 has well-known proliferative and anti-apoptotic effects on monoclonal plasma-cells. Also insulin-like growth factors (IGFs) have been proposed to play a role since obesity often causes insulin resistance, which in turn modulates the bioavailability of IGF-1 Similar to IL-6, prior studies have found IGF-1 to have both growth and survival effects on monoclonal plasma-cells. Based on these facts, we have speculated that obesity might increase the risk of the multiple myeloma precursor monoclonal gammopathy of undetermined significance (MGUS), or, alternatively, that obesity may increase the risk for transformation from MGUS to multiple myeloma. We conducted the first large screening study designed to assess the association between obesity and MGUS among almost 2,000 African-American and Caucasian women. Methods We included 1000 African-American and 996 Caucasian women (age 40-79, median 48 years) from the Southern Community Cohort Study to assess MGUS risk in relation to obesity. Per our sampling strategy, about 50% of the participants were obese. Medical record-abstracted weight and height (measured on the day of study enrollment) and self-reported values had very high concordance (Pearson correlation >0.95). Serum samples from all subjects were analyzed by electrophoresis performed on agarose gel; samples with a discrete or localized band were subjected to immunofixation. Using logistic regression models, we estimated odds ratios (ORs) as measures of risk. Results Among all study participants, 39 (3.9%) African-Americans and 21 (2.1%) Caucasians were found to have MGUS, yielding a 1.9-fold (95%CI 1.1-2.3; p=0.021) higher risk of MGUS among African-Americans (vs. Caucasians). On multivariate analysis, we found obesity (OR=1.8, 95%CI 1.03-3.1; p=0.039), African-American race (OR=1.8, 95%CI 1.04-3.1; p=0.037), and increasing age (quartiles: ≥55 vs. <43 years) (OR=2.5, 95%CI 1.1-5.7; p=0.028) to be independently associated with an excess risk of MGUS. Another interesting finding was that the distribution of the monoclonal immunoglobulin isotype usage among African-American and Caucasian women was significantly different (p=0.007). Their respective rates were: IgG in 79.5% and 71.3 %; IgA in 7.7% and 0%; IgM in 7.7% and 19%; biclonal in 5.1% and 4.7%; and triclonal in 0% and 4.7%. The distribution of serum light-chain types between the two races was also significantly different (P=0.003, chi-square test): kappa in 53.8% and 47.6%; lambda in 43.6% and 42.8%; biclonal 2.6% and 4.7%; and triclonal in 0% and 4.7%. Conclusions Our finding that MGUS is twice as common among obese (vs. non-obese) women, and independent of race, supports the hypothesis that obesity is etiologically linked to myelomagenesis and may have public health impact. The observed 2-fold excess of MGUS among African-Americans (vs. Caucasians) of similar socio-economic status, coupled with other recent studies supports a role for susceptibility genes as the cause for racial disparity in the prevalence of MGUS. Disclosures No relevant conflicts of interest to declare.

Efficacy of Lenalidomide-Based Regimens in Multiple Myeloma Complicated by Extramedullary Plasmacytomas at Relapse or Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4952-4952 ◽  
Author(s):  
Jose Manuel Calvo-Villas ◽  
Adrian Alegre ◽  
Ricarda García-Sánchez ◽  
Miguel T Hernández ◽  
Pilar Giraldo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Bone Lesions ◽  
Complete Disappearance ◽  
Toxicity Profile ◽  
Small Series ◽  
Extramedullary Plasmacytomas

Abstract Abstract 4952 Background Current clinical observations on extramedullary myeloma (EM) are based on small series of relapsed myeloma patients (pts) and, in this situation, results suggest that the disease course is often aggressive. Among novel therapies for extramedullary involvement, thalidomide has provided poor results and bortezomib is emerging as a possible useful drug. The role of lenalidomide for treatment of multiple myeloma (MM) with EM is still under investigation. Aim A multicenter retrospective study was performed by PETHEMA (Spanish Myeloma Group, Spain) to evaluate the response rate and toxicity profile of lenalidomide-based regimens in myeloma patients with extramedullary involvement at relapse or progression. All the cases were evaluated for response of MM and improvement of extramedullary plasmacytoma. Patients and Methods From October 2007 to March 2009, thirteen patients (median age 67 years; range 61–87; 7 females) treated with lenalidomide-containing regimens were recorded. Patients with bone disease without extramedullary manifestations were excluded. Response of MM was evaluated according to the new international criteria and the response of EM by measuring size changes by physical examination, CT scans and/or MR imaging. Adverse events were graded based on the WHO toxicity scale. The M-protein type was IgG in 7 cases, IgA in 5 and light chain in 1. The type of light chain was κ in 7 pts and l in 6. In eight patients the soft-tissue plasmacytomas may have developed from underlying bone lesions [(skull (n=2), rib cage (n=4) and paravertebral (n=2)], two patients had subcutaneous nodules and three had visceral involvement (liver (n=1), lung and kidney (n=1) and pleura (n=1). Multiple localizations were present in 4 pts (30.7%). Six cases (79.6%) received previous antimyeloma treatment for EM before lenalidomide therapy and the incidence of prior bone plasmacytomas was 61.5%. Median time from initial antimyeloma therapy to treatment with lenalidomide was 34 months (range 5 - 115). Median number of prior lines of chemotherapy regimens was 3 (range 1 – 4), including autologous stem cell transplantation in 2 pts, bortezomib-containing regimens in 12 (92.3%) and previous exposure to thalidomide in 1 patient. Ten pts received standard lenalidomide dose (25 mg/day every 4 weeks) plus dexamethasone (40 mg/d PO ranging from 1 to 12 doses/cycle) every 3-week; and three patients received lower doses of lenalidomide and/or different schedules. Involved-field radiotherapy was given in 2 cases. Thirty percent of patients required lenalidomide dose reduction, because of toxicity or intolerance. Results Median duration of lenalidomide treatment was 3.6 months (1 – 15). One case was not evaluable for response because of death from disease progression after one cycle. In nine out of twelve evaluable patients (75%), MM responded to lenalidomide regimens according to EBMT criteria. Three (25%) achieved complete response, five (41.6%) partial response and 1 (8.3%) minimal response. Median time to response was 63 days (range 37 – 180). Regarding EM, nine patients showed response in the size of extramedullary plasmacytomas. Seven (58.3%) achieved complete disappearance of EM and two pts reduction of the size. Response of EM was also achieved in 75% of pts previously exposed to bortezomib, and in 4/9 cases who received therapies for prior extramedullary involvement. Median follow-up period was 6.3 months (1 – 15.8). Median overall survival from the start of lenalidomide therapy was 4.7 months. At the time of analysis, seven patients were still on therapy, and ten (76.9%) were alive. Only one out of the 9 patients who had achieved a response has relapsed so far. Toxicity profile (grade 3/4) was: thrombocytopenia, 4 (30.7%); anemia, 2 (15.3%); neutropenia, 5 (46.4%); neutropenic fever, 1 (7.6%) and others, 3 (11.8%). No deep venous thrombosis (DVT) was reported. Thrombosis prophylaxis was used in most cases (92%) patients. Conclusions We report one of the first investigations specifically evaluating the activity of lenalidomide on EM. Lenalidomide-containing regimens could be an alternative promising approach to achieve clinical response in heavily treated MM patients with extramedullary disease. The duration of response and the best regimen or combination are at present unknown. These preliminary observations require further analysis and longer follow-up. Disclosures No relevant conflicts of interest to declare.

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