Patel, Gaurav

Abstract Abstract 678 Background: Second primary malignancies (SPM) among multiple myeloma (MM) patients have been reported with an estimated incidence varying from 1%–15%. We have previously reported that significant disparity exists in MM survival across patients of different ethnicities. We undertook a Surveillance Epidemiology and End Results (SEER) based analysis to describe the incidence of SPM among MM patients of different ethnicities, in order to explore the variable impact that SPM might have on MM outcomes of patients across racial subgroups. Methods: SEER database was used to examine the standardized incidence rates (SIR) of SPM among MM patients diagnosed between 1973–2008. Observed to expected ratio (O/E) of SPM was calculated using incidence rates of cancers for the general population. The 95% confidence limits (CI) were constructed using Fisher's exact test. The analysis was restricted to patients with MM as first primary, microscopic confirmation of diagnosis, reporting sources not coded as autopsy- or death-certificate-only, and SPM reported more than 2 month after MM diagnosis. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW), Non-Hispanic whites (NHW), and others. The risk of SPM among MM patients was explored by ethnicity, type of SPM, and latency period. Results: A total of 3090 cases of MM with SPM were diagnosed between 1973–2008, of which, 2021 patients met our inclusion criteria. Stratification of SPM by ethnicity revealed: 387 AA (19%), 72 API (4%), 51 HW (3%), 1500 NHW (74%) and 11 other (<1%) cases. There was an average 4.7-year latency period between diagnosis of MM and SPM (mean age 68.2 and 72.9 years, respectively). The latency period was not significantly different by type of SPM (solid organ vs. hematological) or ethnicity. AA had the youngest age at diagnosis for both, MM and SPM (65.6 and 70.1 year, respectively). (Figure 1) For all SPM sites analyzed together, there was no significant difference between the observed and expected incidence (O/E 0.98; 95% CI 0.94–1.02). However, O/E risk was significantly decreased for solid organ SPM (N=1695; O/E 0.92; 95% CI 0.88–0.96) and increased for hematological malignancies (N=263; O/E 1.63; 95% CI 1.44–1.84). Highest excess risk among all SPM was noted for acute non-lymphocytic leukemia (ANLL) (O/E 6.51; 95% CI 5.37–7.83). The overall risk of observed SPM was not different from expected rates by ethnicity, with the exception of HW who had a significantly decreased overall SPM risk. Table 1 summarizes significant results of O/E risk of SPM by race and site. HW and NHW were less likely to develop overall solid organ SPM. Within solid organ sites, HW had a significantly decreased O/E risk of developing lung/bronchus and prostate SPM. NHW were the only ethnic subgroup with an increased O/E risk of developing melanoma of skin, while the O/E risk of developing SPM of kidney/renal pelvis was increased only among AA. The risk of ANLL as SPM was significantly increased among AA, API, and NHW, while risk of NHL as SPM was only increased among NHW. Conclusion: Exploring potential causes of outcome disparities is important for evaluating disease characteristics and optimal triaging of healthcare resources for specific patient populations. We have performed the largest population-based analysis for the risk of SPM in MM patients stratified by race/ethnicity. We found that the risk of developing SPM among MM patients is variable depending on the patient's ethnic background. This warrants further exploration of the impact of SPM on outcomes of MM patients across different racial subgroups. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 845 Background: Waldenstrom's macroglobulinemia (WM) is a relatively uncommon plasma cell disorder and most of previous literature is limited to small patient series. We have noted ethnic disparities in multiple myeloma, another plasma cell disorder. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of WM patients, with a focus on various ethnicities, so that therapeutic resources can be targeted more effectively. Methods: The SEER 17 Registry data (1973–2008) was utilized for patients with confirmed diagnosis of WM. To avoid bias of under representation of different ethnicities, analysis was restricted to patients with a diagnosis date of 1992 or later. Cases that received a diagnosis at death certificate or autopsy, no follow-up records, as well as lacking documentation on age at diagnosis, sex, or race/ethnicity were excluded. Cox proportional hazards models, adjusted for gender, age, race, year of diagnosis, marital status and stratified by SEER registries were used to evaluate associatio n between patient characteristics and survival. All statistical tests were two-sided and utilized the SAS software (v9.2) with a significance level of 0.05. Results: The final analysis included 2,840 WM patients (1,759 males; 62%, 1,081 females; 38%). The studied age-group cohorts included: 18–64 yrs (845; 30%), 65–74 yrs (795; 28%) and >75 yrs (1,200; 42%). Patients were stratified by race/ethnicity: White (2,471; 87%), African-American (AA) (102; 4%), Hispanic (133; 5%), Asian (129; 5%), and Native American (5; 0.1%). Patients were also stratified based on year of diagnosis (before or after 2002) to study the impact of certain novel agents (proteasome inhibitors, IMiDs) on WM treatment. There was a significant difference in the age at diagnosis of WM patients across different ethnicities, with AA the youngest (median 61.5 years) and Whites the oldest (median 73 years) subgroup (p<0.001). (Figure 1) Cause-specific mortality could not be evaluated due to variable documentation of reported causes of death for WM patients in the database. Survival analysis revealed that for all patients, females had better median overall survival (OS) than males (7.3 years vs. 6.2 years, HR 0.834; 95% CI 0.740, 0.939; p=0.003). Among the different age cohorts, patients with age ≥75 years had a significantly worse median OS (4.1 years) than those 65–74 year-old (7.3 years) or 18–64 year-old (10+ years) (p<0.001). Patients diagnosed after 2002 had a significantly better median OS (7.3 years) as compared to patients diagnosed previously (6.1 years) (p=0.002). Hispanics had the worst median OS (5 years) and Whites had the best median OS (6.8 years) across various ethnicities. In a multivariate model using gender, age, marital status, year of diagnosis and race, a significant interaction was noted between race, age and survival, with Hispanics having a significantly worse OS than Whites (HR 1.86; 95% CI 1.269, 2.726; p=0.003) (Figure 2). Conclusions: Studies of outcome disparities are important for evaluating disease characteristics and management needs of specific patient populations as well as optimal triaging of healthcare resources. We have performed the largest population-based analysis for WM including various ethnicities in the novel therapeutic agent era. We observed that AA patients had a significantly younger age at WM diagnosis. Older patients had worse OS across all ethnic subgroups and patients diagnosed after 2002 had a better OS suggesting an impact of novel therapeutic agents (e.g., proteasome inhibitors, IMiDs). Hispanic WM patients had the worst OS among all ethnicities. This survival difference was more significant and pronounced in patients >75 years. This suggests that the impact of race on survival is influenced by patient's age. These results will help in better understanding of various influences on disease biology and clinical behavior. Disclosures: No relevant conflicts of interest to declare.