Multiple Myeloma in the Afro-Caribbean Inner City Population: Conventional Cytogenetics and Survival

Abstract

Background:Multiple Myeloma (MM) is the second most common hematologic malignancy in the United States. African Americans have among the highest risks of MM and MGUS with several distinct features compared to existing literature. Furthermore, the prevalence of MM is even higher in the Afro-Caribbean population. Cytogenetic and molecular genetic abnormalities predict outcome in patients with MM. Hyperdiploid MM (H-MM) generally has a better prognosis than nonhyperdiploid MM (NH-MM). In addition, patients with additional chromosome 1 abnormalities, loss of chromosome 13, translocation t(14;16) and t(4;14) tend to have a worse survival while patients with translocations t(11;14) are associated with improved survival. In our patient population, the most common cytogenetic abnormalities and their effect on survival remain unknown.Objective:This study was performed to establish a profile of Afro-Caribbean patients with newly diagnosed Multiple Myeloma in order to gain further insight into unique cytogenetic abnormalities and their effects on survival.Methods:Patients with Multiple Myeloma at Kings County Hospital Center and University Hospital at Brooklyn from 2000-2013 were identified by our tumor registries (n=311). We included all the newly diagnosed patients from 2000-2013 who underwent a bone marrow biopsy and conventional cytogenetic by chromosome banding and FISH (n= 173). Patients who did not have a cytogenetic analysis were excluded. Data was collected at the time of initial presentation to include demographics and cytogenetic abnormalities. Survival data was obtained from Social Security Death Index. Differences in frequency of each cytogenetic abnormality by mortality status were examined using Chi-Square or Fisher’s Exact Tests. Two sets of age-adjusted logistic regression models were used to examine potential cytogenetic correlates of both poor (less than two years) and good (4 years or more) survival. Data analysis was performed using SPSS Advanced Statistics.Results:The median age at the time of diagnosis was 65 (Range 36-90). Chromosome banding and FISH showed abnormal cytogenetics in 46% of our patients (n=79). These patients were also found to have multiple abnormal clones. NH-MM was found in 24% (n=19) and H-MM was found in 39% (n=31) of the 79 patients. The most commonly affected abnormalities were trisomiesof odd-numbered chromosomes; +1 (47%), +3 (19%), +5 (21%), +7 (24%), +9 (47%), +11 (42%), +15 (44%), +17 (9%) and +19 (29%).Thirty five percent of 173 patients have expired (n=60). The median survival in the deceased patients was 6.2 years (Range 0.34-12.9). When we examined all patients who lived greater than four years post-diagnosis (n=152), we found significant abnormalities including +5 (p=0.052), NH-MM (p=0.009) and t(11;14) (p=0.03) (See Table 1). Indicators of poor prognosis including 1q gain (p=0.13), loss of chromosome 13 (p=0.21) and del17 (p=0.08) were not significant. In patients who are living, 19% (n=29) have not yet reached the four-year post-diagnosis survival. Less than ten percent underwent autologous stem cell transplantation.Excludes patients who lived less than 3 months post diagnosis August 5 2014Table 1:Age-Adjusted Logistic Regression Models Predicting Good Survival (lived 4 years or more post-diagnosis)Chromosome abnormality ( + gain, - loss)Age-Adjusted Odds Ratio (95% CI) N=152P-value1+0.77 (0.26, 2.29)0.631-2.91 (0.58, 14.57)0.193+1.05 (0.35, 3.17)0.935+0.47 (0.22, 1.00)0.0527+0.39 (0.14, 1.10)0.0811+0.80 (0.36, 1.75)0.5714+2.07 (0.62, 6.91)0.2415+0.74 (0.34,1.60)0.4419+1.20 (0.46, 3.13)0.71X-0.42 (0.11, 1.50)0.18Y-0.40 (0.13, 1.26)0.12Hyperdiploidy0.88 (0.39, 2.00)0.88Nonhyperdiplody0.24 (0.08, 0.70)0.009t(4;14)0.76 (0.27, 2.15)0.60t(11;14)0.18 (0.04, 0.86)0.03Conclusion:In this group of Afro-Caribbean patients, median survival (6 years) was higher than Surveillance, Epidemiology, and End Results (SEER) data and more recent review of literature. Gain of chromosome 5 and t(11;14) are consistent with existing data for good prognosis. However, NH-MM which is usually an indicator of poor prognosis was also highly significant in the four-year post-diagnosis survival. This further supports the notion that prognostic value of cytogenetic analysis in this population requires further exploration. DisclosuresNo relevant conflicts of interest to declare.