scholarly journals Analysis of Racial Differences in the Incidence of a Targetable Biomarker, t(11;14), in Patients with Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Fang Liu ◽  
Jeries Kort ◽  
Shashirekha Shetty ◽  
Ravikumar Kyasaram ◽  
John Shanahan ◽  
...  

Introduction Compared with Caucasian Americans (CA), African Americans (AA) have an increased incidence of multiple myeloma (MM), earlier age at diagnosis, and overall better prognosis [1]. The molecular mechanisms underlying such racial disparity are not well understood. Using targeted next generation sequencing assay or traditional fluorescence in situ hybridization (FISH) methods, previous studies reported that t(11;14) is more common in AA compared with CA with MM and monoclonal gammopathies [2,3]. However, the number of AA cases studied were small and conflicting data exists. Clinical trials in relapsed or refractory MM indicate that t(11;14) is a biomarker which may be used to predict response to a therapeutic agent (venetoclax) which targets BCL-2 [4,5]. Identifying racial differences in molecular biomarkers would be helpful in our understanding of the known racial disparities of incidence in MM and in the development of therapeutic trials. Methods 737 patients with newly diagnosed MM or smoldering myeloma (SM) at University Hospitals Seidman Cancer Center between 2009 and 2020 were identified. All had myeloma FISH panel sent at diagnosis, which included trisomy of chromosomes 3, 7, or 11, deletion 13q14.3 or loss of chromosome 13, deletion 17p13.1, 1q21 (CKS1B) amplification, and 14q32.3 rearrangements. IGH/CCND1 [t(11;14)(q13;q32)] dual fusion probe was used prior to 2018. Extra signal would trigger reflex test for IGH/FGFR3 [t(4;14)(p16.3;q32)] and IGH/MAF [t(14;16)(q32;q23)]. IGH break apart probe was used since 2018. IGH rearrangement would trigger reflex testing for translocation partners as listed above. Between-group differences were assessed with T-test for continuous variables, and Chi-square / Fisher's exact test for categorical variables. Results Of the 737 patients (661 MM, 76 SM), 502 (68.1%) were self-reported as CA, 213 (28.9%) were AA, and 22 (3.0%) were of other races or listed as unknown. Median age was 71 among CA and 70 among AA (p=0.67). The male-female ratio was 291/211 (58% male) among CA and 101/112 (47% male) among AA (p=0.0095). Overall t(11;14) was detected in 4.5% of cases, 5.2% CA and 2.8% AA (p=0.165); among 661 MM, t(11;14) was tested positive in 30/656 (4.57%), including 23 (5.1%) CAs, 6 (3.1%) AAs, and 1 others (p= 0.80); among 76 SM, t(11;14) was tested positive in 3/76 (3.95%), all were CAs. The percentages of patients who tested positive for other cytogenetic abnormalities were as follows: trisomy 3,7, or 11 was detected in 35.6% CA and 32.4% AA (p=0.42); 1q21 amplification was detected in 25.5% CA and 23.9% AA (p=0.72); deletion 13q14.3 or loss of chromosome 13 was detected in 16.5% CA and 10.7% AA (p=0.08); deletion 17p13.1 was detected in 6.4% CA and 5.2% AA (p=0.54); t(4;14) was detected in 2.8% CA and 1.4% AA (p=0.27); t(14;16) was detected in 0.4% CA and 0.5% AA (p=0.89) Conclusions This retrospective series of 737 MM and SM patients did not find an increased incidence of the targetable biomarker t(11;14) in AA patients. The overall percentage of t(11;14) cases was lower than expected. The lack of our finding a racial difference differs from some other reports, perhaps due to a fairly enriched AA population. There were also no significant racial differences found in other cytogenetic abnormalities. Further investigation at the molecular level should be performed to elucidate the mechanisms of racial disparity in MM. References [1]. Landgren O, Devesa S, Mink P, et al. African-American multiple myeloma patients have a better survival than Caucasian patients: a population-based study including 28,636 patients. Blood. 2009;114:1832. [2]. Kzandjian D, Hill E, Hultcrantz M, et al. Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients. Blood Cancer J. 2019;9(2):15. [3]. Baughn LB, Pearce K, Larson D, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J. 2018;8(10):96. [4]. Kortüm KM, Einsele H. First targeted therapy in multiple myeloma. Blood. 2017;130(22):2359-2360. [5]. Kumar S, Harrison S, Cavo M, et al. A phase 3 study of venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma. EHA Library. Abstract LB2601. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5337-5337
Author(s):  
Manisha Bhutani ◽  
Preeya Patel ◽  
Myra M Robinson ◽  
Rupali Bose ◽  
Kyle Madden ◽  
...  

Abstract BACKGROUND: Multiple myeloma (MM) is the most common hematologic malignancy in the African American population, with an incidence more than 2 times higher than Caucasian population [Landgren O et al Blood 2006]. Historically, the African American MM patients have had better outcomes compared with other races [Ailawadhi S et al Br J Haematol 2012], but no biologic explanations exist for this observation. Greenberg et al [Blood Cancer J 2015] have recently reported on differences in commonly observed baseline cytogenetic abnormalities (CA) between African American and Caucasian MM patients seen at Mayo Clinic (Rochester, MN), Cook County Hospital (Chicago, IL) and University of Maryland (Baltimore, MD). We examined the MM cohort at our referral center to validate these observations. PATIENTS & METHODS: The Levine Cancer Institute MM database was interrogated for all patients presenting with MM between January 2012 and April 2015. Baseline clinical and pathology variables were compared between the African American and Caucasian cohorts. Continuous variables were compared using nonparametric rank tests, while incidences and proportions (e.g. CAs including t(11;14), t(4;14), monosomy13/del13q and del17p) were compared using Fisher's exact tests. RESULTS: A total of 662 patients were identified; excluding those with MGUS classification, 368 patients were included in the analysis (African Americans n = 130, Caucasian n = 238). The median age of African American MM patients was significantly younger than Caucasian MM patients (median age 60 years vs. 65 years, p=0.010), with similar gender distribution. There was a numerically larger proportion of African American patients with anemia (40.8% vs 30.8%, p =0.166), however, there was no significant difference in degree of BM plasmacytosis amongst the two groups. The overall distribution of MM patients by IMWG risk stratification (Chng et al, Leukemia 2013) was also similar between the two groups. The African American MM patients had a numerically higher incidence of a metaphase abnormality on conventional cytogenetics (21.7% vs. 13.9%, p =0.154). They had a significantly lower incidence of t(11;14) [7.7% vs. 16%, p=0.024], a numerically higher incidence of t(4;14) [6.2% vs. 3.8%, p=0.309], and similar incidence of deletion 13/del13q [22.3% vs. 18.9%, p=NS ] and del17p [7.7% vs. 7.6%, p=NS ]. CONCLUSIONS: The present dataset is the largest single institution report on CA racial differences in MM patients. We found that unlike previous reports of lower incidence of t(4;14) or del17 p in African American MM patients by Greenberg et al, we have observed a higher incidence of t(4;14) and similar incidence of del17p in our experience compared to Caucasian MM patients. The different pattern of CA distribution compared to published literature may represent geographic heterogeneity and potentially influence survival outcomes. Disclosures Cogdill: Celgene: Speakers Bureau; Onyx: Speakers Bureau; Millennium: Speakers Bureau; Novartis: Speakers Bureau. Usmani:Celgene: Honoraria, Speakers Bureau; Onyx: Honoraria, Research Funding, Speakers Bureau; Janssen Oncology: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Pharmacyclics: Research Funding; Millennium: Honoraria, Speakers Bureau; Array BioPharma: Honoraria, Research Funding.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Pratik Bhattacharya ◽  
Ambooj Tiwari ◽  
Sam Watson ◽  
Scott Millis ◽  
Seemant Chaturvedi ◽  
...  

Background: The importance of early institution of “Do Not Resuscitate” (DNR) orders in determining outcomes from intracerebral hemorrhage is established. In the setting of acute ischemic stroke, African Americans tend to utilize critical care interventions more and palliative care options less than Caucasians. Recent epidemiological studies in acute ischemic stroke have shown a somewhat better survival for African Americans compared with Caucasians. Our hypothesis was that racial differences in early institution of DNR orders would influence mortality in acute ischemic stroke. Methods: a retrospective chart review was conducted on consecutive admissions for acute ischemic stroke across 10 hospitals in Michigan for the year 2006. Subjects with self reported race as African American or Caucasian were selected. Demographics, stroke risk factors, pre morbid status, DNR by day 2 of admission, stroke outcome and discharge destination were abstracted. Results: The study included 574 subjects (144 African American, 25.1%; 430 Caucasian, 74.9%). In-hospital mortality was significantly higher among Caucasians (8.6% vs. 1.4% amongst African Americans, p=0.003). More Caucasians had institution of DNR by day 2 than African Americans (22.5% vs. 4.3%, p<0.0001). When adjusted for racial differences in DNR by day 2 status, Caucasian race no longer predicted mortality. Caucasians were significantly older than African Americans (median age 76 vs. 63.5 years, p<0.0001); and age was a significant predictor of DNR by day 2 and mortality. In the adjusted analysis, however, age marginally influenced the racial disparity in mortality ( table ). Caucasians with coronary disease, atrial fibrillation, severe strokes and unable to walk prior to the stroke tend to be made DNR by day 2 more frequently. Only 27.1% of Caucasians with early DNR orders died in the hospital, whereas 20.8% were eventually discharged home. Conclusions: Early DNR orders result in a racial disparity in mortality from acute ischemic stroke. A substantial proportion of patients with early DNR orders eventually go home. Postponing the use of DNR orders may allow aggressive critical care interventions that may potentially mitigate the racial differences in mortality.


Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3849-3856 ◽  
Author(s):  
John Shaughnessy ◽  
Joth Jacobson ◽  
Jeff Sawyer ◽  
Jason McCoy ◽  
Athanasios Fassas ◽  
...  

Abstract Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo–13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo–13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo–13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4547-4547
Author(s):  
Deimante Tamkus ◽  
Ahmad Jajeh ◽  
Ebenezer Berko ◽  
David Osafo ◽  
Decebal Griza ◽  
...  

Abstract Inferior survival of African American and Hispanic patients with acute lymphoblastic leukemia (ALL) has been reported. The reason for this is unclear. A retrospective analysis was conducted to see if abnormal cytogenetics account for the differences. We have analyzed cytogenetic studies of 39 adults (16 year and older) with newly diagnosed ALL who were consecutively treated at John Stroger Hospital of Cook County between 1997 and 2005. The study population included 13 (33%) African Americans, 18 (46%) Hispanics, 6 (16%) Caucasians, and 2 (5 %) other ethnic background adults. Male to female ratio was 2:1. Mean age at diagnosis was 26 (range between 16 and 71 years). A clonal cytogenetic abnormality was detected in 27 patients, and 12 patients had normal karyotype. Patients with t (9;22)(q34;q11), BCR-ABL + by FISH, t (4;11)(q21;q23), +8, −7 cytogenetic abnormalities were assigned to an unfavorable cytogenetic group. This group was composed of 14 patients. None of our study patients had favorable cytogenetics: del (12p), t(12p), t(14q11-q23), inv(14)(q11;q32) or t(10;14)(q24;q11). Remaining 25 patients with normal karyotype (n=12) or miscellaneous cytogenetic abnormalities (n=13) were classified as normal risk group. 54 % of African Americans had unfavorable cytogenetics, compared with 33 % Caucasians and 17 % Hispanics. Translocation t (9;22) alone or in association with other cytogenetic abnormalities was most commonly seen. 9 patients had single, and 18 had multiple chromosomal changes. Hispanic group had more complex cytogenetic changes when compared with the African American or Caucasian groups. Unfavorable cytogenetic abnormalities may account for inferior survival in African Americans, but other factors such as compliance or pharmacogenetics should be evaluated, especially in the Hispanic patient population.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3081-3081 ◽  
Author(s):  
Michele Cavo ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
...  

Abstract Aim of the present sudy was to evaluate the benefit of novel agents combined with conventional therapies in multiple myeloma (MM), with particular emphasis on patients (pts) carrying adverse cytogenetic abnormalities. For this purpose, we analyzed a series of 142 pts who received thalidomide-dexamethasone (thal-dex) and double autologous transplantation (double Tx). By study design, thal-dex was administered from the outset until the second autologous Tx. On an intent-to-treat basis, stringently defined (immumofixation negative) complete remission (CR) rate following double Tx and thal-dex was 54%. This value was significantly higher (P=0.0009) compared to the 33% observed in a comparable series of 129 pts who received double Tx without thal-dex. In comparison with these latter patients, addition of thal-dex to double Tx significantly prolonged PFS (median: 31 vs 42 months; P=0.04) and did not adversely affect survival after post-transplant relapse (P=0.7). All 142 pts included in the study were investigated at baseline for the presence of chromosome 13 deletion [del(13)] by FISH analysis and of t(4;14) using a RT-PCR assay. An analysis on an intent-to-treat basis performed according to the presence or absence of these cytogenetic abnormalities revealed that the probability to respond (more than 90% reduction in M protein concentration) to primary therapy with thal-dex for 94 pts who carried both del(13) and t(4;14) was significantly lower compared to that of 69 pts with del(13) alone (12% vs 41%, respectively; P=0.012) and of 18 pts with t(4;14) alone (12% vs 50%, respectively; P=0.006). The lower probability of response to first-line thal-dex therapy conferred by the presence of both del(13) and t(4;14) was completely offset by subsequent application of double Tx and thal-dex. Indeed, on an intent-to-treat basis, the probability to attain a very good partial response or CR for pts with both del(13) and t(4;14) positivity was 68% compared to 80% for pts with both del(13) and t(4;14) negativity (P=0.1). With a median follow-up of 24 months, the 3-year projected probabilities of OS and PFS were 80% and 59%, respectively (intent-to-treat). The presence or absence of t(4;14) had no significant impact on the 3-year projected probability of OS (80.12% vs 80.42%, respectively; P=0.3). Furthermore, an analysis of pts who actually received thal-dex and double Tx showed that curves of OS and EFS were almost superimposable among pts who carried or lacked both del(13) and t(4;14). Indeed, the 3-year projected probability of OS for pts with both these cytogenetic abnormalities was 92% compared to 88% for pts who were negative for both del(13) and t(4;14); (P=0.7); the corresponding figures for EFS were 70% vs 77%, respectively (P=0.9). These results suggest that thal-dex combined with double Tx may overcome the unfavourable prognosis conferred by del(13) and t(4;14). A longer follow-up is required before definite conclusions can be drawn.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 8033-8033
Author(s):  
Nathanael Fillmore ◽  
Sarvari Yellapragada ◽  
Paul S. White ◽  
Chizoba Ifeorah ◽  
Mahmoud Gaballa ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17099-e17099
Author(s):  
Eirwen M Miller ◽  
Joan Tymon-Rosario ◽  
Xianhong Xie ◽  
Harriet Olivia Smith ◽  
Gary L. Goldberg ◽  
...  

e17099 Background: Studies demonstrate racial disparity in ovarian cancer survival though survival differences seem to be mitigated when patients receive similar care. We sought to identify whether racial disparity exists in the use of NAC or PDS for women with ovarian cancer. Methods: After IRB approval, all patients with epithelial ovarian cancer who received primary treatment at our institution from 2005-2016 were identified from our tumor registry. Charts were retrospectively reviewed for clinicopathologic and survival data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Kaplan-Meier was used to compare survival probabilities. Results: 302 evaluable patients were identified. 240 (79%) patients underwent PDS and 62 (21%) received NAC. Older patients, black patients, and those with stage III/IV disease were more likely to receive NAC. In a multivariate analysis controlling for stage and age, black race remained associated with NAC [OR 3.25 (95% CI 1.41-7.47), p < 0.01]. In a subgroup of advanced disease, stage III patients (n = 138) were more likely than stage IV patients (n = 52) to undergo PDS (78% v 44%, p < 0.01) and black patients were more likely than others to present with stage IV disease (39% v 22%, p = 0.01). NAC was utilized more frequently (48% v 24%, p < 0.01) in black patients compared with all other races. In the advanced stage subgroup analysis, patients that underwent PDS had a longer PFS than those that received NAC [HR 2.21 (95% CI 1.26-3.89), p = 0.01]. Conclusions: Racial disparity exists in the selection of PDS compared with NAC for patients with ovarian cancer and this disparity persists when controlling for stage and age. The choice of NAC or PDS may result in survival disparity. Further investigation is needed to examine other reasons, such as medical co-morbidities and disease distribution, for racial disparity in management. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18140-e18140
Author(s):  
Anne Renteria ◽  
Sundar Jagannath ◽  
Kezhen Fei ◽  
Sylvia Lin ◽  
Radhi Yagnik ◽  
...  

e18140 Background: Multiple Myeloma (MM) management has significantly improved disease-free and overall (OS) survival but disparities among racial groups still exist. After the Affordable Care Act, the extent to which induction, autologous stem cell transplant (ASCT), and maintenance therapies are used are uncertain. We sought to describe underuse of induction, ASCT and maintenance in a large referral center. Methods: Between 2010 and 2014, 3101 patients were diagnosed with MM via ICD-9 code from the Data Warehouse and certified hospital tumor registry. NCCN 2014 and CMS guidelines were used to define the categories of treatment underuse, and define transplant eligibility. Demographics including insurance, Charlson Comorbidity Index and treatments received were determined via chart abstraction. To date, 393 confirmed MM from 697 charts were abstracted. Comparison by groups used Chi-square for categorical variables, t-test and ANOVA for continuous variables. Multivariate logistic regression models were applied to predict underuse of induction, harvest, ASCT, and maintenance. Results: Patients were 62 ±11.3 years-old, with no racial differences in age and insurance coverage. More minorities had Medicaid (Black [B] 13%, White [W] 7%, Hispanic [H] 25%; p = 0.001). Almost all patients (97%) received induction (B 99%, W 96%, H 100%; p = 0.3), with no difference by insurance. Among transplant eligible patients, 93% underwent harvest, 87% underwent ASCT, with no racial differences. Patients with Medicare or self-pay were less likely to undergo harvest compared to patients with Medicaid or private insurance (p = 0.01). No difference in ASCT rates by insurance were noted. B patients were less likely to receive maintenance than non-B (73% vs 86%; p = 0.03), with no difference by insurance. OS was 73%, with no racial differences. In multivariate model, older age predicted induction underuse (aOR = 1.15, 95% CI: 1.06-1.25) (c = 0.9, p = 0.005), and B patients experienced more maintenance underuse (aOR = 2.22, 95% CI: 1.09-4.54) (c = 0.61, p = 0.1), controlling for age and comorbidity. Conclusions: While there were no racial or insurance differences in access to induction therapy, fewer Black patients received maintenance therapy. Interviews are underway to understand reasons for observed differences.


2015 ◽  
Vol 5 (2) ◽  
pp. e279-e279 ◽  
Author(s):  
A J Greenberg ◽  
S Philip ◽  
A Paner ◽  
S Velinova ◽  
A Badros ◽  
...  

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