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Cardiac stage and depth of hematologic remission are major predictors of survival for AL amyloidosis patients (Wechalekar et al., Blood, 2013; Dispenzieri et al., JCO, 2004; Palladini et al., JCO, 2012). Renal staging in AL amyloidosis (AL) has been studied in the context of renal survival (Palladini et al., Blood 2014). Influences on survival for renal patients have yet to be fully defined. We performed a retrospective study of all AL patients with renal involvement diagnosed at our center between 7/1/08 and 6/30/15. In this cohort of consecutive patients (n=80) median age was 63 (IQR 55-70) and 56% were men. Eighty-eight percent had lambda plasma cell disease and median involved FLC was 140mg/L (69-485). Thirty-nine percent were renal stage 1, 44% stage 2, and 16% stage 3. Median 24-hour proteinuria and serum creatinine were 6.23 g (3.47-10.70) and 1.03 mg/dL (0.80-1.80) respectively, and median eGFR was 72 mL/min (41-90). Fifty-eight percent had cardiac involvement, of whom 11% were cardiac stage 1, 54% stage 2, and 34% stage 3, while 18% had GI and 9% peripheral nerve involvement. As first-line therapy, 70% received bortezomib-based regimens and 25% melphalan-based autologous stem cell transplant. By intention-to-treat, at 6 months after beginning therapy, 54% of patients had a hematologic response of PR or better, and renal and cardiac responses occurred in 13% and 14% of patients respectively, while renal progression occurred in 6%. Median overall survival (OS) for this cohort (n=80) was 67 months. Those with cardiac involvement (n=45) had a median OS of 41 months and, while median OS was not reached for cardiac stage ≤ 2, it was 31 months for those who were stage 3 (P In conclusion, for AL patients with renal involvement, both cardiac stage and depth of hematologic response are important contributors to overall survival. Furthermore, as this real world intention-to-treat analysis demonstrates, there is a continuing need for better therapies for both the hematologic disease and the organ damage associated with AL. Figure. Figure. Disclosures Oliver: Prothena Biosciences, Inc.: Employment, Equity Ownership. Guthrie:Prothena: Employment, Equity Ownership, Other: Leadership. Comenzo:Takeda: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Karyopharm: Research Funding; Janssen: Consultancy, Research Funding.

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 2014 | Chromosome abnormality ( + gain, - loss) | Age-Adjusted Odds Ratio (95% CI) N=152 | P -value | | ------------------------------------------------ | ---------------------------------------------- | -------- | | 1+ | 0.77 (0.26, 2.29) | 0.63 | | 1- | 2.91 (0.58, 14.57) | 0.19 | | 3+ | 1.05 (0.35, 3.17) | 0.93 | | 5+ | 0.47 (0.22, 1.00) | 0.052 | | 7+ | 0.39 (0.14, 1.10) | 0.08 | | 11+ | 0.80 (0.36, 1.75) | 0.57 | | 14+ | 2.07 (0.62, 6.91) | 0.24 | | 15+ | 0.74 (0.34,1.60) | 0.44 | | 19+ | 1.20 (0.46, 3.13) | 0.71 | | X- | 0.42 (0.11, 1.50) | 0.18 | | Y- | 0.40 (0.13, 1.26) | 0.12 | | Hyperdiploidy | 0.88 (0.39, 2.00) | 0.88 | | Nonhyperdiplody | 0.24 (0.08, 0.70) | 0.009 | | t(4;14) | 0.76 (0.27, 2.15) | 0.60 | | t(11;14) | 0.18 (0.04, 0.86) | 0.03 | Table 1: Age-Adjusted Logistic Regression Models Predicting Good Survival (lived 4 years or more post-diagnosis) Conclusion: 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. Disclosures No relevant conflicts of interest to declare.

Multiple Myeloma (MM), a plasma-cell neoplasia characterized by bone marrow (BM) infiltration, monoclonal protein production, and end organ dysfunction, is the most common hematologic neoplasm in blacks. The subclinical syndrome monoclonal gammopathy of undetermined significance (MGUS) precedes MM, and SEER data as well as more recent reports show that blacks have a 2-3-fold higher risk of developing MGUS and MM suggesting a genetic predisposition that causes the marked racial disparity in the incidence of both conditions. In addition, the recent rate of survival improvement observed in Caucasian patients has not been observed in blacks implying that the clinical course and development of resistance are varied between black and Caucasian MM patients. We have recently reported that in our inner-city, largely Caribbean-African patients MM occurs more frequently in women and at a younger age compared to literature. In this report we present cytogenetic information on 146 of these newly-diagnosed MM patients and their survival data. Patients were identified by tumor registries at UH and Kings County Hospital based on tumor histopathology. Data were collected from hospital records of patients treated between 2001-2011 (n=242).Downstate’s inner-city MM patients in Brooklyn, NY are largely Caribbean-African individuals and descendants. Demographics, disease indicators, and vital statistics were collected. In 146 patients, baseline cytogenetics by chromosome banding studies were available. In 63 of these patients baseline FISH used locus-specific probes del13 (13q14), IGH translocation (14q32), del17 and t(11;14)(q13;q32). Patients were treated with standard combination therapies. 146 patients had active, advanced newly-diagnosed MM. Median age=66 (range 36-91), male/female= 0.8, and evidence for the degree of tumor burden included: median % infiltration with CD138-positive cells within BM=50% (range 7%-99%), median serum M protein 3.3 g/dL (range 0.2-9.1). International Staging System level: Stage II: 28%, Stage III: 72%; median serum creatinine=2 mg/dL (range 0.38-14), median serum beta-2 microglobulin= 5.8 mg/dl (range 0.96-20.2). Further, 58% of patients with cytogenetic information had diffuse skeletal involvement with multiple lytic lesions (48%) and fractures (10%). Contrary to expectations from patients with advanced MM, chromosome banding and FISH showed abnormal cytogenetics (AC) in only 26% (n=38). At present, 50% of the patients have expired in both the normal cytogenetics (NC) and AC groups. In the AC group who expired, average time with MM was 2 years (range 0.5-5.6), whereas in the NC patients, average survival was 3.4 years (range, 0.6-5.2). Frequency of trisomies 5 and 9 indicative of hyperdiploidy, were twice as common in patients who are surviving with AC. In these latter patients as well as in surviving patients with NC, average survival time with MM is 4 years (range 0.4-15). In addition, IGH translocation was twice as common in AC patients who expired compared to the NC group. Other AC findings including hypodiploidy, del13, chr1 loss, and trisomies involving chromosomes 1, 7, 11, 19, and 21 were equally frequent in expired and living patients with AC. Using clinically available methods we found IGH translocation, trisomy 5 and trisomy 9 to be prognostically significant in this cohort of 145 inner-city, largely Carribean-African patients. Subtle presentation of cytogenetic abnormalities suggest that genome-wide analyses are needed to asses this patient populations’ MM biology.Cytogenetic Abnormality (frequency)Alive (n)Expired (n)Mean Survival in Years of Expired Patients with AC (Range)del 13 (12.3%)8101.2 (0.1-3.6)IGH translocation (13.0%)7121.7 (0.1-4.1)Chr 1 gain (8.2%)571.1 (0.1-2.4)Chr 1 loss (4.8%)342.3 (0.5-4.1)Hyperdiploidy (19.9%)15141.8 (0.1-5.6)Hypodiploidy (8.9%)761.7 (0.1-4.1)Trisomy 5 (12.3%)1261.7 (0.1-5.6)Trisomy 7 (6.9%)641.2 (0.5-2.3)Trisomy 9 (15.1%)1482.1 (0.1-5.6)Trisomy 11 (12.3%)992.0 (0.1-5.6)Trisomy 15 (11.6%)1161.5 (0.1-5.6)Trisomy 19 (13.7%)1371.7 (0.1-4.1) Disclosures: No relevant conflicts of interest to declare.