Yang, Dongyun

600 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with a high mortality burden. Lenvatinib is an effective frontline tyrosine kinase inhibitor for HCC but is associated with primary and acquired resistance in most patients. Molecular mechanisms of resistance to lenvatinib remain unclear. Methods: We retrospectively analyzed 227 patients with HCC who underwent baseline ctDNA profiling as a component of routine clinical care, including 46 patients who had serial ctDNA analysis done at baseline and after progression to lenvatinib or ICI. Clinical data including demographics, treatment history, tumor responses, and survival outcomes were abstracted from the electronic medical record. Tumor response was categorized according to RECIST 1.1. A national registry of HCC that underwent ctDNA testing using Guardant360 was analyzed to determine the prevalence of EGFR/ERBB2 alterations in HCC. Results: Nearly a third of patients who progressed on lenvatinib demonstrated a gain in EGFR/ ERBB2 amplifications or activating mutations. No consistent trend in EGFR/ ERBB2 amplifications and alterations was found among ICI refractory HCC. Disease control rates (including complete response, partial response, and stable disease) were 20% in EGFR/ERBB2 altered HCC treated with lenvatinib, 62.5% in EGFR/ERBB2 wildtype HCC treated with lenvatinib (p = 0.05), and 58% in EGFR/ERBB2 altered HCC treated with ICIs (p = 0.09). PFS was also longer in EGFR/ERBB2 wildtype HCC treated with lenvatinib (5.9 months) and EGFR/ERBB2 altered HCC treated with ICIs (7.1 months) compared to EGFR/ERBB2 altered HCC treated with lenvatinib (2.2 months, p = 0.002). In a national cohort of 1739 patients with HCC, EGFR amplifications and activating mutations occurred in 6.5% and 1.5% of cases, respectively, and ERBB2 amplifications and activating mutations occurred in 1.9% and 0.7% of cases, respectively. Among EGFR/ERBB2 mutations, we identified recurrent gatekeeper mutations, including multiple A547T and T790M mutations, in 31% of patients. Conclusions: Our study substantiates EGFR/ERBB2 amplifications and mutations as putative drivers of lenvatinib resistance in patients with HCC and identifies the genetic mechanisms for EGFR pathway activation in refractory cancers. EGFR/ERBB2 alterations may thus represent predictive and pharmacodynamic markers of lenvatinib resistance. These findings lend support to the use of EGFR inhibitors combined with lenvatinib in previously untreated or lenvatinib refractory cancers.

3590 Background: Co-occurring alterations (COAs) in the HER2 and MAPK pathway are rare in mCRC. RAS, HER2 and BRAF alterations have been associated with resistance to EGFR inhibitor therapy (EGFR-mab). Typical co-occurring mutually exclusive gene mutations such as in KRAS and BRAF have been reported. This study aims to evaluate the prevalence of co-occurring alterations in the MAPK pathway or across MAPK/ HER2 and correlate to outcomes in patients with mCRC treated with EGFR-mab. Methods: This is a retrospective study of patients with mCRC within the Mayo Clinic database who have available blood-based NGS Guardant 360 data (September 2017-November 2021) and contained co-alterations in the MAPK pathway or across MAPK/ HER2. MSI-high cases were excluded. Typical-RAS was defined as alterations in codons 12, 13, 59, 61, 117, and 146 of KRAS, HRAS, and NRAS. Atypical-RAS alterations were considered mutations at other codons of these genes. Patient characteristics, specific mutations, and outcome data were assessed. Results: 692 patients (pts) with mCRC were identified and 66 (9.5%) of those had COAs detected. 59/66 pts had clinical data available. Median age was 52 years, 55.9% were male, and 61.0% had left-sided tumors. The frequency of detected alterations was: BRAF-V600E (7.3%), BRAF-non-V600E (7%), BRAF-amplification (3.04%), RAS-typical (39.5%), RAS-atypical (2.1%), HER2 amp (0.5%), HER2-mutation (1.2%) and PIK3CA (13%). COAs are described in the table. Twenty-three pts received EGFR-mab; COAs developed in 19 of them after progression on EGFR-mab. Four pts received EGFR-mab with documented COAs at baseline with none of them responding to treatment. Conclusions: COAs in MAPK and MAPK/ HER2 pathway are not uncommon in pts with mCRC emphasizing on the importance and feasibility of blood based NGS vs. selected gene testing. In pts with prior EGFR-mab treatment, COAs were detected after progression on treatment in the majority of pts, suggesting a mechanism of secondary treatment resistance. Further data including prospective validation is warranted. [Table: see text]

Abstract Background: NK/T cell non-Hodgkin lymphomas (NK/T NHL) are rare high-grade lymphomas that are diagnostically challenging and carry a poor prognosis. Incidence is notably higher in Asian countries as compared to North America and Europe. South Americans have an incidence similar to Asian countries though less well described. In this study we reviewed the incidence and outcomes of NK/T NHL in the US with a specific focus on patient race/ethnicity. Methods: Surveillance, Epidemiology and End Results (SEER) database was used to examine the standardized incidence rates (SIR) of NK/T cell NHL among adult (≥18 yrs) patients diagnosed between 1992-2013. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW) and Non-Hispanic whites (NHW). Cases that received a diagnosis at death certificate/autopsy, no follow-up records, or lacking age at diagnosis, sex, or race/ethnicity documentation were excluded. Age adjusted incidence rates (AAIR) were calculated by race. Cox proportional hazards models, adjusted for confounding variables, were used to evaluate association between patient demographics and overall survival (OS). Results: A total of 706 cases met inclusion criteria. Of these, 64% were males and 36% females. AAIR was higher in males irrespective of race/ethnicity. Among different race/ethnic subgroups, API and HW had a higher AAIR than NHW and AA (0.2, 0.18, 0.05 and 0.04, respectively) (Figure 1). Median OS for males and females was similar (1.8 yr and 2 yr, respectively; p=0.76) There was a statistically significant difference in median OS by age for all patients with 4.3 yr for age 18-44 as compared with 0.8 yr for age >75 yr (p<0.001). Median OS by was different for HW (1.3 yr), API (1.8 yr), AA (2.3 yr) and HW (2.5 yr) but did not reach statistical significance (p=0.45). Median OS by stage varied as 7.3 yr for stage IE to 0.9 yr for all other stages combined (p<0.001) Cases with disease location as nasal cavity or sinus had a median OS of 3.5 yr as against 1.1 yr for those with all other sites (p<0.001) (Table 1). Conclusions: Significant disparities exist in the US for NK/T NHL incidence by race and gender, with highest AAIR among the racial minorities of API and HW, which are fastest and second fastest growing minority groups in the US respectively. Increasing age, advanced disease stage and site outside of the nasal cavity or sinus are independent predictors of poor prognosis. Some differences do exist in survival by race. These factors need to be considered for better resource allocation and utilization for this rare, often incurable and aggressive disease. Figure 1 Figure 1. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Kelly:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

Abstract Background: As of 2013, approximately 558,340 people are living with non-Hodgkin lymphoma (NHL). Outcome disparities have been reported in lymphoid malignancies but a comprehensive analysis, especially with expanding ethnic minorities is necessary. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of T-cell and B-cell NHL patients (pts), with a focus on various ethnicities. Methods: The SEER 18 Registry data (1973-2011) was utilized for pts with a confirmed diagnosis of T-cell or B-cell NHL. Cases that received a diagnosis at death certificate or autopsy, no follow-up records, no documented age at diagnosis, sex, or race/ethnicity were excluded. Cox proportional hazards models, adjusted for gender, age, race, year (yr) of diagnosis, and stratified by SEER registries were used to evaluate association between pt characteristics and survival. All statistical tests were two-sided and utilized the SAS software (v9.4) with a two-sided significance level of 0.05. Results: The final analysis included 7,662 pts with T-cell NHL and 84,910 pts with B-cell NHL. The pt demographics are shown in Table 1. Pts were stratified based on yr of diagnosis to study the impact of therapeutic developments on pt outcomes (Table 1). Pts were also divided by T-cell NHL subtype: mature T-cell (9702/3) 51%, angioimmunoblastic T-cell (9705/3) 16%, anaplastic large cell (ALCL) (9714/3) 32%, and hepatosplenic gamma-delta cell (HSϒd) (9716/3) 0.8%. Median age at diagnosis was youngest for AA pts (54 yrs) and oldest for Asian pts (65 yrs) (Figure 1 A). Survival analysis revealed that females had a better median OS than males (3.3 yrs vs. 2.3 yrs, HR 0.876; 95% CI 0.824, 0.932; p<0.001). Increasing age was an independent predictor of worse overall survival, with pts age 18-44 having a median OS 9.4 yrs (HR 0.345; 95% CI 0.312, 0.382) and pts age ≥75 having a median OS of 1.0 yr (p<0.001). There was no statistically significant difference seen in median OS for pts with respect to yr of diagnosis (p=0.081). Among the different T-cell NHL subtypes, pts with ALCL had the best (3.8 yrs, HR 0.766; 95% CI 0.714, 0.822) and pts with HSϒd had the worst median OS (0.7 yrs HR 1.959; 95% CI 1.424, 2.695) (p<0.001). AA pts (1.7 yrs, HR 1.292; 95% CI 1.176, 1.419) and Hispanic pts (1.9 yrs, HR 1.215; 95% CI 1.087, 1.357) had significantly worse OS compared to White pts who had the longest median OS (3.1 yrs) (p<0.001) (Figure 1 B). To compare and contrast with aggressive B-cell NHL, similar analyses were performed using diffuse large B-cell (DLBCL) NHL (9680/3). DLBCL showed similar trends regarding sex, age and race. Ethnic minorities had significantly worse median OS including Hispanic (2.8 yrs, HR 1.154; 95% CI 1.111, 1.198) and AA pts (3.3 yrs, HR 1.261; 95% CI 1.212, 1.312) compared to White pts with a median OS of 5.8 yrs (p<0.001). B-cell NHL pts had a significant improvement in median OS over time with pts diagnosed in 2007-2011 having more than 3 times the median OS of pts diagnosed in 1973-1991 (7 yrs vs. 2.4 yrs; p<0.001). Conclusions: Studies of outcome disparities are important for evaluating disease characteristics and their relationship to specific pt populations over time. We have performed the largest population-based analysis for T-cell and B-cell NHL including various ethnicities in the novel therapeutic agent era. We observed that males, older pts and ethnic minorities had worse median OS for both T-cell and B-cell NHL. Despite novel therapeutics targeting T cells there has been no statistically significant improvement in OS over time. In contrast, significant improvement in B-cell NHL OS has been noted, presumably due to the advent of monoclonal antibodies. These results underline the urgency for the development of novel therapeutics as well as aggressive studies of disease biology and healthcare utilization for better triage of healthcare resources, especially for ethnic minorities. Table 1. Table 1. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Background Outcomes for patients with chronic myeloid leukemia (CML) have improved in recent years. Nonetheless, survival disparities persist between various patient subgroups. There have been limited reports of ethnic variations in CML outcomes, with limited data on ethnic minorities (Hispanics and Asians), who are the fastest growing ethnic subgroups in the Unites States. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of CML patients, with a specific focus on various ethnicities. Methods SEER 17 Registry data (1973-2010) was utilized. Adult (>18 years) patients with confirmed diagnosis of CML were eligible. To avoid bias of under representation by ethnic minorities, analysis was restricted to patients with a diagnosis date of 1992 or later (SEER expansion). Cases that received a diagnosis at death certificate/autopsy, no follow-up records, or lacking age at diagnosis, sex, or race/ethnicity documentation were excluded. Cox proportional hazards models, adjusted for confounding variables, were used to evaluate association between patient characteristics and overall survival (OS). All statistical tests were two-sided with a significance level of 0.05, utilizing the SAS software (v9.2). Results The final analysis included 10,356 CML patients (5,943 males; 57.4%, 4,413 females; 42.6%). Age group cohorts included: 18-44 years (2,592; 25%), 45-54 years (1,706; 16.5%), 55-64 years (1,817; 17.6%), 65-74 years (1,876; 18.1%), and ≥75 years (2,365; 22.8%). Patients were stratified by race/ethnicity: White (7,292; 70.4%), African-American (AA) (1,143; 11%), Hispanic (1,163; 11.2%), Asian (697; 6.7%), and Native American (61; 0.6%). For survival analysis, Native Americans were excluded due to their small numbers. Patients were also stratified based on year of diagnosis (1992-1999, 2000-2004 and 2005-2010) to study the impact of evolving therapeutics on CML outcomes. Median age at diagnosis was significantly different among ethnicities (p<0.001) with Hispanics the youngest (47 years) and Whites the oldest (63 years) (Figure 1). There were more Hispanic and AA CML patients reported in recent years in the database than those in 1992-1999 or 2000-2004 (p<0.001). Survival analysis revealed that for all patients, females had a significantly better median OS than males (7.8 years vs. 6.4 years; p<0.001). Among the different age cohorts, median OS got progressively worse with increasing age at diagnosis (p<0.001), with a median OS of 15+ years in 18-44 year cohort vs. 2.3 years in patients ≥75 years. Patients diagnosed more recently had a better median OS (1992-1999: 4.5 years vs. 2000-2004: 7.7 years vs. 2005-2010: 9.8 years; p<0.001). AA had the worst median OS among all ethnicities, which was significantly worse than Whites (reference) (5.8 years vs. 7.4 years; p<0.001). Asians had a median OS of 6.4 years and Hispanics 6 years. In a multivariate model using race, age at diagnosis, year of diagnosis, sex and marital status, a significant interaction was noted between year of diagnosis and race, with all racial subgroups showing improvement in 5-year survival in more recent time periods (p=0.001) (Figure 2). A significant interaction was also noted between year of diagnosis and age, with a progressive improvement in 5-year survival noted across all age groups in more recent years (p<0.001) (Figure 3). Conclusions We present a population-based study of outcomes in CML with the largest representation of ethnic minorities reported so far. We noted a higher number of AA and Hispanic patients reported to the SEER database in recent years. Hispanic patients had a significantly younger age at diagnosis, which could mean longer treatment duration over the lifetime of a patient. AA patients had the worst median OS among all ethnicities, although all ethnicities and age groups were noted to have progressive improvement in outcomes in more recent years of diagnosis. The incremental benefit in outcomes was seen most for Asians and least for Whites. These results will help in better understanding of ethnic influences on disease biology and clinical behavior as well as optimal triaging of healthcare resources. Disclosures: Off Label Use: The abstract shows scientific information on SAR245409 which is an investigational product developed by Sanofi. This investigational product is not approved by any health authority for any indication.

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.

Abstract Background: The incidence of secondary Acute Lymphoblastic leukemia (sALL) after a preceding first primary solid organ malignancy (1M) is not well defined. We undertook a Surveillance Epidemiology and End Results (SEER)-based analysis to describe the occurrence of sALL among adult patients with a history of common 1M's. We also evaluated differences in sALL survival on the basis of age, the site and extent of 1M, and for evidence of any underlying racial/ethnic disparity. Methods: The SEER-18 database (1973-2011) was interrogated for the current study. All confirmed cases of ALL (ICD-O-3 codes: 9811, 9812, 9814-18, 9826-28, 9835-37) in adult patients (age ≥18 years) were identified. De novo ALL vs. sALL was determined by using the SEER variable ‘First Malignant Primary Indicator'. 1M prior to the diagnosis of ALL was identified by merging all SEER databases together by patient ID number. Those with 1M stage of ‘in situ'; sALL cases reported <2 months after the diagnosis of 1M; and those with “unknown” information on 1M (n=471) were excluded. Standard race/ethnicity categories were used. Latency interval (time from diagnosis of 1M to sALL) was calculated for all patients. Overall survival (OS) was calculated as the interval from diagnosis to death, or censored at date of last contact, December 31st 2011, or 5 years after diagnosis, whichever came first. A proportional hazards Cox regression model was performed to evaluate the impact of sALL and latency on OS, adjusting for age at diagnosis, race/ethnicity, marital status, birthplace, SEER registry site, and year of diagnosis. All statistical tests were two-sided and utilized the SAS software (v9.4) with a two-sided significance level of 0.05. Results: A total of n=8,398 adult patients with primary ALL (1ALL) and n=414 with sALL were identified. Patient characteristics were significantly different between 1ALL & sALL (Table). Males comprised 49.8% of sALL patients as compared to 58% with 1ALL. Age at diagnosis of ALL was also significantly different, with 55.5% of sALL patients being ≥65 years as compared to 51.4% of 1ALL observed in the 18-44 years age group. Non-Whites comprised 27.3% of sALL and 40.4% of 1ALL, with Hispanics having the most differential distribution of 13.3% and 24.6%, respectively in the two groups. Distribution of sALL patients by latency from 1M is shown in Table. The majority of sALL patients had a diagnosis of local/regional (rather than advanced stage) 1M (Table). sALL patients had a significantly inferior OS when compared to 1ALL (HR 1.211, 95%CI 1.079-1.359) (Median OS 14 months vs. 18 months, Figure). sALL cases with longer latency interval (>5 year) appeared to have better median OS compared to shorter latency intervals, but this difference was not statistically significant (p=0.53). Conclusion: We have performed the largest population-based analysis identifying sALL after 1M, demonstrating that sALL patients are older and have significantly worse OS than 1ALL. We noted a lower relative incidence of sALL in Hispanics as compared with 1ALL, while the converse was true for Whites. Although detailed treatment data (specifically with respect to chemotherapeutic agents) is not available in SEER, it is possible that treatment for local/regional 1M - presumably adjuvant in nature - may be associated with the risk of sALL. Further analyses are required and are ongoing to confirm the relative incidence after specific 1M's, and the impact of both specific treatment modalities and the era of treatment for 1M on risk of developing sALL. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Background: We have previously reported on ethnic disparities in outcomes of multiple myeloma (MM) pts (pts) and shown that Hispanics have the shortest median overall survival (OS) and myeloma-specific survival (MMS) while Asians have the longest. Ethnic minorities are increasing in number in the United States (US) and have been historically underrepresented in population databases with limited follow up since the introduction of novel agents for MM. We did an updated analysis with longer follow up for ethnic minorities to explore the changes in outcomes by race and also explored MM incidence rates, not reported previously. Methods: Surveillance Epidemiology and End Results (SEER) 13 Registry data (1973-2013) for adult pts (>18 yr) with confirmed diagnosis of MM was utilized. To avoid bias of under representation of ethnic minorities, analysis was restricted to pts diagnosed in 1992 or later. Years of diagnosis were 1992-1995 (pre-stem cell transplant; SCT), 1996-2002 (after SCT but before novel therapeutics) and 2003-2013 (after introduction of novel therapeutics). Cases that received a diagnosis at death certificate/autopsy, without follow-up records, lacking documentation on age at diagnosis, sex, or race/ethnicity were excluded. Cox proportional hazards models were used to evaluate association between patient characteristics and survival. All statistical tests utilized the SAS software (v9.4) and were two-sided with a significance level of 0.05. Results: The final analysis included 68431 MM pts (37300 males; 55%, 31131 females; 45%). Age-group cohorts included: 18-44 yr (2519; 4%), 45-54 yr (8131; 12%), 55-64 yr (15416; 23%), 65-74 yr (20214; 30%), and ≥75 yr (22151; 32%). Mutually exclusive racial subgroups included: non-Hispanic White (NHW; 44618, 65%), non-Hispanic African-American (AA; 13164, 19%), non-Hispanic Asian/Pacific Islanders (API; 3570, 5%), Hispanic (H; 6759, 10%) and Native American (NA; 320, 0.5%). Trends in age-specific incidence rates were similar for all races but except the 20-24 yr group, were highest for AA and lowest for API. (Figure 1) Survival analysis showed that females had a better median OS (3.4 vs 3 yr; p<0.001) and MMS (4.7 vs 4.4 yr; p<0.001) than males. Age was an independent predictor of OS (p<0.001) with the median OS changing from 7.3 yr in 18-44 to 1.9 yr in ≥75 age group. Similar results were seen for age groups and MMS as well (p<0.001). During the three pre-specified time periods for year of diagnosis, both the median OS and MMS progressively improved (P<0.001) suggesting improved outcomes secondary to treatment advancements. H and AA had the worst median OS (3.1 yr) as compared to NHW and API (3.3 yr) (p<0.001) and H had the worst median MMS (4.3 yr) while API had the best (5.1 yr) (p<0.001). Survival analyses were performed for ≥75 age group separately since it was the largest and traditionally with worst outcomes. The difference in median OS by gender was still significant (p<0.001) but less pronounced (1.8 vs 1.9 yr) and was not significant for MMS (p=0.33). Due to less SCT utilization, no incremental OS or MMS benefit was seen prior to advent of novel agents but since 2003 the ≥75 group did have a small benefit for OS (2 vs 1.6 yr, p<0.001) and MMS (3 vs 2.3 yr, p<0.001). Race no longer predicted for a statistically significant OS difference (p=0.52) while for MMS, H continued to have the worst (2.5 yr) and NA the best (3.8 yr) outcome (p<0.001). 5-year relative survival rates (RSR) over time showed an incremental improvement in recent years for all racial groups except API ≥70 yr (Figure 2) with generally an increased incremental benefit for the <70 yr age group than the elderly. For majority of races no incremental benefit was seen in 5-yr RSR for ≥70 yr pts between 1992-1995 and 1996-2003 but improvement was seen in 2004-2013. Conclusions: In a fast changing US demographic mix, significant disparities for MM incidence and outcomes exist by race/ethnicity. As compared to our previous analyses, new trends have emerged with Whites having an improved median OS than AA while H continue to have the worst MMS and API the best. Differences in median OS among races are no longer significant in elderly pts. A modest benefit in OS is being seen for elderly pts since the advent of novel therapeutics. Studies of ethnic disparities are important for evaluating management needs of specific patient populations as well as optimal triaging of healthcare resources. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Kelly: Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Speakers Bureau. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.

Abstract Abstract 757 Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia seen in adults. Previous population-based research in CLL has not represented the current ethnic makeup and diversity within the US population. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to assess disparities in outcome among different ethnic subgroups of CLL patients, so that therapeutic resources can be utilized effectively. Methods: The SEER-18 Registry (1973–2009) was used to retrieve a population of 60,293 patients with established diagnosis of CLL (Histology code: 9823). The cohort was restricted to adults (>18 yrs) diagnosed after January 1, 1992, since ethnic minorities were underrepresented in SEER prior to that. Cases reported in death certificate/autopsy, those without a confirmatory diagnosis, those with ethnicity recorded as unknown/other or those that did not have follow up post diagnosis were excluded. Using Cox proportional hazards models, adjusted for confounding variables, association between patient characteristics and survival (overall; OS and CLL-specific; CLLSS) was evaluated. Analysis was performed utilizing the SAS software (v9.2). All statistical tests were two-sided with a significance level of 5%. Results: A total of 37,834 patients (22,581 males; 60%, 15,253 females; 40%) were included in the final analysis. Age group (yr) cohorts included: 18–44 (861; 2%) 45–54 (3,587; 9%), 55–64 (7,684; 20%), 65–74 (10,966; 29%), and ≥75 (14,736; 39%). For survival trends over time, stratification by year of diagnosis was used: 1992–1999 (9,837; 26%), 2000–2004 (14,129; 37%), 2005–2009 (13,868; 37%). Stratification by race/ethnicity included: White (32,980; 87%), African-American (AA: 2,486; 7%), Hispanic (1,536; 4%), Asian (737; 2%), and Native American (NA: 95; 0.25%). Median age ranged from 68 yr (AA and Asian) to 71 yr (Whites) (Figure 1). For survival analysis, NA ethnic group was excluded due to their small numbers. Females had a significantly better median OS (8.3 yr vs. 6.4 yr; p<0.001) as well as CLLSS (p<0.001) than males, when evaluated for the whole population and across different age groups. Both, OS and CLLSS progressively and significantly (p<0.001) declined with advancing age. Progressive significant improvement was seen in OS over time across cohorts by year of diagnosis (6.3 yr, 7.3 yr, 7.4 yr; p<0.001). This improvement in OS persisted over time for age groups <75 yr, but for ≥75 yr, the improvement was lost in the most recent time period cohort (2005–2009). The percentage of patients dying of CLL has decreased progressively over time suggesting an improvement in therapy. Among various ethnicities, Asians had the best (7.5 yr) and AA had the worst (4.8 yr) OS (p=0.006) (Figure 2) and CLLSS (p<0.001). In a multivariate model, AA continued to have the worst OS across all age groups (p<0.001), while Whites had the best OS in age groups <75 yr and Asians had the best among patients ≥75 yrs. Percentage of patients dying from CLL was highest in AA across age groups, but lowest for Whites in age groups <75 yr, while in Hispanics in patients ≥75 yr. Trends in CLLSS were noted to be more heterogeneous among ethnicities than trends in OS. Conclusions: This report presents the largest population-based analysis of patient characteristics including ethnicity and survival in CLL in the era of novel therapeutic agents. Older patients had worse OS among all ethnic subgroups. Progressive improvement in CLLSS was noted over time suggesting a possible impact of new therapeutics, however this was not seen in ≥75 yr patients. AA patients had the worst OS among all ethnicities and age groups. This survival difference was most significant and pronounced in younger patients, which has important implications. For example, this survival disadvantage may represent poor access to optimal healthcare warranting development of new initiatives directed towards this ethnic minority. On the other hand discrete biological variants may underlie the more aggressive disease biology in younger AA patients underscoring the need to further investigate and delineate the molecular biology of CLL in ethnic minorities. Studies of outcome disparities are important not only for evaluating disease characteristics but also management needs of specific patient populations and are critical for designing programs to deliver optimal healthcare to ethnically diverse populations. Disclosures: No relevant conflicts of interest to declare.