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Background: Median age at diagnosis for MM is 69 years with approximately 33% of the newly diagnosed MM (NDMM) patients aged ≥80 years (elderly). Yet, outcomes data and clinical trial participation in elderly MM patients are limited due to frailty and frequent comorbidities. Moreover, elderly patients are not candidates for stem cell transplant (SCT) and age is an independent poor prognostic marker, leading to disparate outcomes. The present study evaluated trends in outcomes and predictors of survival among elderly NDMM patients in the United States (U.S.). Methods: Using Surveillance Epidemiology and End Results (SEER) database, we extracted data on age, gender, geographical regions, year of diagnosis, and vital status for elderly patients (age ≥ 80 years) with MM from 1975 to 2016. Relative survival (RS) was estimated as the ratio of observed survival to the survival expected in the general population in the absence of malignancy. This adjusted for the competing causes of mortality prevalent in elderly patients. Mortality rates were age-adjusted. To estimate trends in mortality, we estimated annual percentage change (APC) and average annual percentage change (AAPC) by fitting the data in the join point regression model using the NCI's Join point Regression Program, Version 4.5.0.1. A multivariate analysis was conducted to analyze the predictors of overall and myeloma-specific mortality among elderly patients fitting into Cox proportion hazard regression model. Results: A total of 17,265 elderly MM patients were eligible for the study. Majority were females (n=9,487, 55%), were non-Hispanic whites (NHW) (n=12,895, 74.7%) and were diagnosed in the Western region of the U.S. (n=8,541, 49.5%). The median age was 84 years (IQR 81-87). The median RS for the whole period (1975-2016) was 19.8 months with 1- and 5- year RS of 60.1% (95%CI: 58.8-61.3) and 20.9% (95%CI: 19.5-22.3) respectively. The median RS increased from 8.45 months in 1975 to 29.86 months in 2013. One and 5- year RS also increased from 42.7% (95%CI: 32.4-52.5) and 12.9% (95%CI: 5.8-22.7) in 1975 to a 1- and 5-year RS of 72.3% (95%CI: 65.4-78.1) and 31.1% (95%CI: 23.4-39.1) in 2013, respectively (Fig.1). However, the age standardized mortality rate for the whole period showed an increasing trend with an AAPC of 2.3 (0.5-4, P Conclusions: Our results suggest that although RS has improved significantly in the elderly patients, the mortality rates have not changed drastically over the years. Besides, factors like advancement in diagnosis and treatment which have improved RS, early diagnosis (leading to lead time bias) may also be contributing. Furthermore, there are several gender-specific, geographic and racial/ethnic disparities in outcomes of elderly MM patients, which need to be assessed prospectively. Although, a small decline in mortality rates in the more recent time is promising, further studies are warranted on interventions including aggressive supportive care directed at elderly patients with MM, so that MM survivorship can be improved. There should be strong consideration to increaseenrollment of the elderly in prospective clinical trials so that evidence-based guidelines can be developed. Disclosures Manochakian: Takeda: Membership on an entity's Board of Directors or advisory committees; Guardant Health: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Novocure: Membership on an entity's Board of Directors or advisory committees. Chanan-Khan:Merck: Research Funding; Ascentage: Research Funding; Millennium: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Pharmacyclics: Research Funding; AbbVie: Research Funding; Xencor: Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy, Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding. Off Label Use: Do not remove- this information is relevant to Abstract ID 125629: TAK-169 is a dimeric fusion protein of an anti-CD38 antibody single chain variable fragment fused to a modified Shiga-like toxin-A subunit..

Background: HIT has the potential to improve the health of individuals and the performance of providers, yielding improved quality, cost savings, and greater engagement by patients. Minorities face a variety of financial and nonfinancial barriers to obtaining appropriate and timely health care. Studying the behavior of minority patients will help understand the specific challenges to HIT adoption and engagement in patients and their caregivers. We undertook a patient-reported survey to explore these factors and understand any underlying disparities. Methods: A 21-question paper-based anonymous questionnaire addressing the responder's attitudes, understanding and needs of the electronic medical record (EMR) was used. This was administered to adult patients with lymphoid malignancies and their caregivers at two campuses of Mayo Clinic in Florida (San Pablo and inner-city; Riverside). Categorical and continuous variables between white and minority responders as well as minority responders from the two campuses were compared using the Chi-square test and U Mann Whitney with a significance level of 0.05. Results: The survey was completed by 1004 patients and caregivers. Average time taken to complete the survey was approximately 11 minutes. Of the responders, 716 (71%) were whites and 271 (27%) were minorities, with race-ethnicity not reported by 17 (2%). Among minorities, 30% (n=80) were seen at San Pablo and 64% (n=173) at the Riverside campus, with 6% at a multiple myeloma patient-caregiver symposium. Whites were older (median age 66 vs. 62 years, p Conclusions: Minorities continue to struggle with suboptimal utilization of healthcare system including that of HIT. There are barriers related to access, awareness, language and understanding of HIT that prevent the integration and participation of racial-ethnic minorities in the healthcare system to a full extent. It is important to qualify the minorities better, since there exist HIT utilization disparities even within the minorities from different areas representing socioeconomic and demographic differences. Efforts need to be made at several levels to help the minorities overcome educational, access and linguistic barriers so that they can benefit from advancements in the healthcare system. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Takeda: Consultancy. Manochakian:Novocure: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Guardant Health: Membership on an entity's Board of Directors or advisory committees. Chanan-Khan:AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding.

INTRODUCTION: Patients undergoing HSCT are reported to have a high prevalence of depression and anxiety. These comorbid mood disorders have been known to be associated with alteration in pain perception in patients without hematological malignancies. Pharmacological compounds such as opioid and benzodiazepines are frequently used to manage patient symptomology including pain and anxiety. Patients undergoing HSCT are a unique population where the impact of depression and anxiety on opioid and benzodiazepine use has not been well studied. METHODS: The study population consisted of patients who underwent HSCT at a single center for a variety of hematological malignancies from 2015-2018. Opioid and benzodiazepine exposure and dosage was defined in a) Patients who were exposed to opioid including those who were previously exposed and those who were exposed during hospitalization for HSCT b) Patients who were neither exposed to opioid previously, nor during the hospitalization for HSCT. Depression and Anxiety was defined as per PHQ-9 and GAD-7 scales prior to hospital admission. Multivariable analysis was performed to identify differences in opioid status, previous benzodiazepine use, transplant type, Karnofsky score, gender, age, race, and marital status with associated Diazepam Equivalent Daily Dosage (DEDD) (Negative Binomial Regression), and Morphine Milligram Equivalent Daily Dosages (MMEDD) (Logistic and Zero Truncated Negative Binomial Regression). RESULTS: A total of 275 patients underwent HSCT including autologous and allogeneic from 2015-2018. Anxious or depressed HSCT recipients had an increased incidence of higher DEDD with an IRR of 1.69 (95% CI: 1.15, 2.49) compared to those who were neither depressed nor anxious (Figure 1). However, patients who reported anxiety and depression did not have a different DEDD than those not anxious nor depressed. In addition, patients who were not naïve to benzodiazepine use prior to admission had an increased incidence of a higher DEDD [IRR of 2.23 (95% CI: 1.61, 3.05)]. Patients undergoing autologous stem cell transplant had a decreased incidence of receiving a higher DEDD [IRR of 0.65 (95% CI: 0.47-0.90)]. African American and other populations had a decreased incidence of receiving a higher DEDD [IRR of 0.40 (95% CI: 0.27, 0.59)]. Patients receiving higher MMEDD had a higher DEDD incidence [IRR of 1.01 (95% CI: 1.01, 1.02)]. Patients who were both anxious and depressed had increased odds of receiving an opioid [OR of 3.35 (95% CI: 1.62, 6.94)] compared to patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared to those who were neither depressed nor anxious. Patients undergoing autologous stem cell transplant had reduced odds of receiving an opioid [OR of 0.17 (95% CI: 0.07, 0.40)]. Patients with less than normal Karnofsky performance status ( Finally, HSCT recipients who were both anxious and depressed had reduced odds of being naïve to opioids [OR0.31 (95% CI: 0.15, 0.67)] compared to recipients who were neither depressed nor anxious. New opioid users had reduced odds of receiving a greater MMEDD [OR of 0.98 (95% CI: 0.96, 0.99)] when compared to previous users. In addition, autologous stem cell transplant recipients had reduced odds of receiving greater MMEDD compared to allogeneic transplant recipients (OR 0.33, 95% CI: 0.16, 0.66). CONCLUSION: Comorbid depression and /or anxiety impact opioid and benzodiazepine use in patients undergoing HSCT. The presence of these comorbid conditions and their association with increased use of opioids and benzodiazepines can also affect various health related outcomes. Larger studies are needed to fully understand the potential impact of this association on health related outcomes. Figure 1. Figure 1. Disclosures Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Seattle Genetics: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy.

Background: Multiple myeloma (MM) is characterized by the invasion of malignant plasma cells into the bone marrow. While first line treatment options result in significant clinical benefit to patients, spatiotemporal clonal evolution results in disease relapse and mortality. Advances in genomics have armed clinicians with unprecedented insight into the molecular architecture of MM cells, however, the clinical benefit derived by genomics-guided intervention has been limited. We present a novel computational biology modelling (CBM) tool, which takes into account the combined effect of individual mutations, gene copy number abnormalities and large scale chromosomal changes in order to predict the salient molecular pathways utilized by the MM cell for survival. By reverse-engineering MM cell architecture in silico, the CBM tool is able to predict drug response and resistance mechanisms. Thus, our aim was to determine the accuracy of the CBM tool in predicting treatment response of relapsed/refractory MM patients for future management of their disease, in a more individualized manner. Methods: Cytogenetics and somatic mutations (by targeted NGS) for 15 MM patients were input into the CBM model to predict responses to different therapeutic combinations. All patients were relapsed to prior treatment. CBM uses PubMed and other online resources to generate patient-specific protein network maps of activated and inactivated disease pathways. We simulated the specific combinations of the drugs per patient and measured the quantitative drug effect on a composite MM disease inhibition score (i.e., cell proliferation, viability, apoptosis and paraproteins). The actual clinical outcome of the treatments was compared with predicted outcomes. Results: Fifteen patients were analysed using CBM for prediction of treatment response after NGS was performed. 13/15 were clinically evaluable, of which 1 was a responder and 12 were non-responder. 6/13 patients were treated on clinical trial and 7/13 were on drug combinations per physician decision. CBM correctly predicted 1 responder and 11 non-responder with a PPV of 50%, NPV 100%, specificity 91.67%, sensitivity 100%. The accuracy of CBM prediction was 92.30%. CBM also predicted the response of prior drug therapies for its non-response at relapse. For prior drug treatment options, 14 patients were evaluable. All the 14 patients were clinically non-responders and CBM correctly predicted for 13 patients with NPV 100%, Specificity 92.85% and overall accuracy of 92.85%. The majority of patients did not respond to therapies recommended at relapse. As an example, the operative molecular pathways from 2 patients who did not respond to combination treatment, either pre-NGS or post-NGS profiling, are shown in Fig. 1 and Table 1. CBM identified amplification (AMP) of chromosome (chr) 1 (WNT3A, IL6R, CKS1B, MCL1, PIK3C2B, USF1), chr 3 (HES1, PIK3CA, CTNNB1, WNT7A, FANCD2), chr 5 (IL6ST, IRF1, GLRX, SKP2), chr 7 (CDK5, EZH2, IL6, CAV1, ABCB1), chr 9 (NOTCH1, HSPA5, FANCC, FANCG), chr 15 (DLL4, FANCI, ALDH1A2), chr 19 (ERCC1, ERCC2, USF2); deletion(DEL) of chr 13 (CUL4A) , chr 16 (AXIN1, CDH1) and TP53 mutation in different combinations, which confer resistance to therapies at relapse. Conclusions: The CBM technology represents a potential means to identify therapeutic options for MM patients based on the patients individual tumor-genome profile and which can also be deployed for uncovering drug resistance mechanisms. This tool may aid clinicians in decision making for recommending the most appropriate therapy based on standard of care agents or clinical trials; thus improving patient outcomes and reducing unnecessary costs or drug-related toxicities. Disclosures Singh: Cellworks Research India Private Limited: Employment. Sauban:Cellworks Research India Private Limited: Employment. Husain:Cellworks Research India Private Limited: Employment. Kumar:Cellworks Research India Private Limited: Employment. Kumari:Cellworks Research India Private Limited: Employment. Tyagi:Cellworks Research India Private Limited: Employment. Abbasi:Cell Works Group Inc.: Employment. Vali:Cell Works Group Inc.: Employment. Ailawadhi:Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this. Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis. Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. Disclosures Ailawadhi: Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

Background: Therapeutic advancements have led to significant improvement in outcomes for MM patients. Revised diagnostic criteria from International Myeloma Working Group focus on initiating treatment before the onset of end-organ damage. Thus, timeliness of initial therapy can significantly improve patient morbidity and outcomes. Such an analysis has not been reported for MM. Methods: We analyzed patients diagnosed with MM between 2004-2015 from the National Cancer Database (NCDB). Patients who received systemic treatment any time within the first year of diagnosis were included; those treated later than one year were considered possibly initially diagnosed with smoldering myeloma and hence, excluded. Time to initial treatment was divided into centiles with the 4 centiles analyzed being 0-7 days, 8-18 days, 19-37 days and >37 days. We performed univariate and multivariate analyses to compare sociodemographic and clinical factors influencing patient distribution across these timeliness categories and trends over time. Results: A total of 53,665 patients were included with 15,282 in 0-7 days, 12,462 in 8-18 days, 12,723 in 19-37 days and 13,198 in the >37 days treatment categories. Distribution across these centiles over time is shown in Figure. Univariate analyses showed a significant difference in distribution across the timeliness categories by year of diagnosis, patient age, gender, race/ethnicity, education level, insurance type, comorbidity score, treatment facility type, geographical location and distance to treating facility (all p37 days to treatment) for women (p0 Charlson comorbidity score (p Conclusions: Several factors were found to affect timeliness of treatment in MM. We noted relatively faster time to initial treatment in elderly, uninsured or those who were treated in academic/comprehensive cancer programs but a delay in treatment for women and racial/ethnic minorities among other factors. These factors need to be addressed for equitable access and treatment practices and to realize improved outcomes for all. Figure. Figure. Disclosures Ailawadhi: Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

INTRODUCTION: Significant burden of pain syndromes are reported in patients with hematological malignancies undergoing HSCT mostly due to underlying disease and associated treatments. Opioid analgesics and benzodiazepines are routinely used for symptomatic management in this patient population. The use of narcotic analgesics and benzodiazepines in non-transplant hospitalized patients has been shown to adversely affect health related outcomes such as length-of-stay (LOS), falls and other complications. However, there is a significant knowledge gap regarding the patterns of opioid and benzodiazepine use and their impact on health outcomes in HSCT patients. METHODS: We identified 275 patients from the year 2015-2018 who underwent HSCT (allogeneic and autologous transplants) at our center for a variety of hematological malignancies. Opioid exposure was defined in three groups of patients 1) Opioid naïve: those did not report prior use of opioid at admission and who were not prescribed opioid during hospitalization, 2) Previous Opioid users: those who reported active use of opioid at admission and continued during hospitalization 3) New Opioid users: Patients who did not report opioid use at admission but were prescribed opioid during hospitalization. Multivariable analysis was performed to identify differences in opioid status, opioid use, benzodiazepine use, disease diagnosis, Karnofsky score, gender, age, race, and marital status with associated complications (Poisson regression), emergency department visits (Logistic Regression) and length of stay (Ordinal Logistic Regression) Figure 1 and Figure 2. RESULTS: The median age of patients was 59 (range: 25-74 ) years with slight male predominance (57%). Patients undergoing autologous transplants for multiple myeloma (MM) comprised 48% of the population. The majority (72 %) were exposed to opioid during hospitalization. Ninety two percent of the opioid naïve population (28% of the total population) underwent autologous transplant. Conversely, 36% of patients undergoing autologous transplants never received opiates during hospitalization as compared to 7% of those who received an allogeneic transplant. Median morphine milligram equivalent daily dose was 3.1 mg. Median diazepam equivalent daily dosage in patients that were opiate exposed was 2.07 milligram. Of the total transplant population, 55% received benzodiazepine concurrently with opiates during hospitalization. 76 % of the population was exposed to both opioid and benzodiazepine. Twenty five percent of those who were exposed to opioid did not receive benzodiazepines. Sixty four percent of the MM patients were exposed to opioid of which majority (59%) were previous opioid users. Of the non-MM patients undergoing HSCT, 80% were exposed to opioid of which 36% were previous opioid users and 64% were new users. A wide range of complications from neutropenic fever to death, were seen in 89% of all patients (opioid users and non-users) but all the falls occurred in patients who were on opioid medications. Autologous transplant recipients had higher odds of having a greater number of complications compared to Allogeneic transplant patients (OR 1.25, 95% CI: 1.01 - 1.55, p=0.04), as well as a reduced odds of having a medium or high length of stay (OR 0.03, 95% CI: 0.02 - 0.07). Of the opioid naïve patients, 6% presented to the ED within 30 days of discharge versus 15% of those that were exposed to opiates during hospitalization. Benzodiazepine use at admission for HSCT was associated with greater odd of presenting to ED within 30 days of discharge (OR 3.94, 95% CI: 1.55-10.04) and this was more significant in patients with MM (OR 4.08, 95% CI: 1.01-16.44). Finally, we also saw a trend towards longer stay in patients who were exposed to opioids as compared to opioid naïve (40% vs. 17%). CONCLUSION: Our study, albeit limited due to its retrospective design, is among the first to report the patterns of use and the impact of opioids and benzodiazepines in patients undergoing HSCT. Our results indicate that the use of these medications is frequent in this population and as in the non-transplant hospitalized patients and is associated with more emergency room visits post discharge, along with other potentially adverse outcomes. Disclosures Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Seattle Genetics: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy.

Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

Introduction: CLL is a heterogeneous disease where advanced stage pts have compromised survival despite treatment, while early stage pts may not require any intervention. Based on current NCI-WG guidelines, most early stage (Rai stage 0 and 1) CLL pts do not require treatment until the development of progressive or symptomatic disease, though eventually over 70% of CLL pts will receive therapy. Currently, there are no markers to predict this subset of pts. Several markers of adverse prognosis, including ZAP-70+, CD38+, un-mutated IgVH gene and cytogenetic aberrations (17p-, 11q-, +12) have been identified. These markers are primarily studied in context of aggressive clinical course and survival outcome. The value of these markers to predict the necessity of treatment intervention in early stage CLL pts has not yet been completely evaluated. We investigated the expression pattern of Zap-70 and CD38 to examine their predictive value in identifying early stage CLL pts who will require therapeutic intervention. Methods & Results: 93 CLL pts were evaluated since 2002 at our institution. Flow cytometry was used to determine Zap-70 and CD38 expression on CD19+ CLL cells obtained from peripheral blood. Pts were considered to be positive for Zap-70 and CD38 expression if ≥ 20% and ≥ 30% of the cell stained for these proteins, respectively. For the Zap-70 analysis we used similar methodology as described by Crespo et al.1 Thirty-six (19M, 17F) pts had limited stage CLL, based on Rai staging criterion. Median age was 65 years (range 43–86) with stage 0 or 1 observed in 14 and 22 pts, respectively. Median time from diagnosis is 2 years (range Conclusion: Our study, demonstrates for the first time, the clinical utility of CD38 and Zap-70 co-expression in determining the probability of treatment intervention in early stage CLL pts. Although the number of pts studied is small, our findings highlight a potentially important use of these markers in the management of early-stage CLL pts. These observations warrant validation in a larger cohort of pts early stage CLL pts as well as correlation with other prognostic markers such as cytogenetic and IgVH gene mutational status.

Introduction: T is an effective antimyeloma therapy. An important and problematic side effect of T is development of VTE. The underlying etiology of T associated VTE remains unknown, though a definite rise in its incidence is recorded when combined with other antimyeloma therapies such as dexamethasone (15%) and doxorubicin (26%). Defining an optimal way to prevent T associated VTE is important to improve patient’s quality of life and safety of T. We prospectively investigated the use of weight-adjusted, low-dose warfarin to decrease the incidence of VTE among pts treated with T based regimens. Methods: All pts treated with T-based therapies, at our institute were given VTE prophylaxis with 1 vs. 2mg warfarin for actual body weight Results: A total of 80 pts, 60 years (range 43–82), 35M and 45F are included in this analysis. Sixty three had stage III and 14 had ≤ stage II MM while 3 pts had WM. T was given with dex in 58 (72%) with dox in 57(71%) and with bortezomib in 32 (40%). Table 1 outlines the T based regimens used. IgG MM was noted in 39, IgA in 20 and 31 had other types of MM. Median T dose was 200 mg (range 50–300) and the median duration 4 months (range 1–6 months). Thirty two pts received 1mg and 48 received 2mg warfarin. Overall incidence of VTE was 6.25% (n=5). There were no bleeding complications noted with the use of warfarin in this pt population. Conclusion: Our study demonstrates for the first time that a weight adjusted low-dose warfarin approach in MM pts decreases the incidence of T associated VTE and can be safely instituted in pts treated with this important anti-myeloma therapy. Interestingly, none of the pts who received T with Doxil experienced any episode of VTE. Regimen No. of Patients Thalidomide Alone 1 Dexamethasone + Thalidomide 28 Bortezomib + Doxil + Thalidomide 24 VAD + Thalidomide 22 Bortezomib + Cyclophosphmaide + Dexamethasone + Thalidomide 5

Introduction: Extramedullary plasmacytomas are malignant plasma cell tumors that arise outside of the bone marrow. They occur either as solitary tumors with a cure rate of over 95% with radiation therapy alone; or they may present as manifestations of advanced metastatic multiple myeloma, referred to as secondary extramedullary plasmacytomas (SEP). SEP usually present as multiple tumors, primarily in the head and neck area and often after multiple relapses in MM patient. Although the etiology of multiple SEP remains unknown, they are reflective of clinically advanced disease that no longer relies on the bone marrow microenvironment. The incidence, clinical outcome and natural history of SEP are not clearly delineated in the literature. With the recent use of novel therapies (thalidomide, lenalidomide, bortezomib) resulting in prolonged survival we have noticed an increase incidence of patients relapsing with SEP at our institute. This observation prompted us to formally evaluate SEP to characterize the clinical pattern of presentation, clinical course and correlation with use of novel therapies of SEP. Methods: This is a single institute retrospective review. All patients seen at our institute with the diagnosis of MM were evaluable. Data was queried since 1990, which included a total of 343 patients. Results: To date 100 patients have been reviewed and among these, 20 patients (20%) were noted to have SEP. Characteristics of these patients are outlined in details in table (1). 14 patients (70%) remain alive. However, none achieved a complete remission after the diagnosis of SEP. Conclusion: In this study, the overall incidence of SEP was 20% on the patients so far evaluated. Majority of SEP patients have received prior novel agents. Systemic treatments seem to be effective in controlling progression of SEP though achievement of CR status has not been possible with current therapeutic interventions. Our finding are intriguing as the incidence of SEM seems to be increasing, which may reflect either unveiling of the natural history of the disease through improved survival from the use of novel agents, or this may be reflective of a change in the biology of MM. We intend to present the complete analysis of all cases at the meeting. Characteristics of patients with secondary plasmacytoma Characteristics Sex 8 (40%) and 12 (60%) F Age Median: 66, Range(46–86) Stage 16(80%) stage III and 4(20%) < stage III Type 9(45%) IgG,6(30%) IgA, 4(20%) Free Light Chains and 1 (5%) nonsecretory Prior treatments 19(95%) had prior Thalidomide or Bortezomib,17(85%) had prior Thalidomide and12(60%) had prior Bortezomib Locations of Plasmacytomas 5(25%) Head&Neck,7(35%) Paraspinal, 2(10%) Abdomen,4(20%) Thorax and 2(10%) at other locations

Introduction: Use of bisphosphonate (zoledronic acid and pamidronate) for prevention of pathological fractures is standard of care in multiple myeloma (MM) patients with osteolytic bone lesions. While clinical trials have investigated effectiveness of these agents for up to 2 years of use, clinical practice has incorporated their use indefinitely. With improvement in survival through availability of novel agents in MM patients, the use of bisphosphonate therapy has also prolonged. Recent reports unveiled a new side effect of Bisphosphonate therapy i.e., ONJ, characterized by necrosis of the jawbone with antecedent subluxation or loss of the teeth and ulceration of the gum mucosa. The underlying etiology remains elusive, and in the absence of effective remedy ONJ has raised significant concerns upon the duration of treatment with Bisphosphonate. We investigated the magnitude of this problem among MM patients receiving Biphosphonate therapy at our institute. Methods: We conducted a retrospective review of all patients diagnosed with MM at our institute since 2001 who received bisphosphonate treatment and developed ONJ. Clinical characteristics, prior treatments and renal function prior to development of ONJ were evaluated. Results: Records of 20 pts who developed ONJ were reviewed. The median age of these pts was 57 (range 45–69). Among these, 9 were males, 11 were females. All pts (100%) had stage III MM. 11 patients (55%) received 2 or more antimyeloma treatment. 14 pts (70%) were on Zoledronic acid, 5 pts (25%) were on Pamidronate, and 1 pt (5%) was first on Zoledronic acid then switched to Pamidronate. Out of those 20 patients, 19 (95%) had normal renal function prior to and after development of ONJ, with Creatinine level range of (0.5–1). Only 1 patient (5%) had decreased renal function prior to development of ONJ, with Creatinine level of 6.6 Conclusion: Although the number of patients reported are small, experience at our center with ONJ in MM patients who were on Bisphosphonate failed to show any association with renal function. Interestingly all patients who developed ONJ were stage III MM. There are currently no established guidelines for prevention or treatment of this disorder.

Background: Tumor microenvironment (ME) plays an important role in MM. It is associated with disease progression, metastasis, and resistance to therapy. Therefore, targeting the ME and the tumor cell simultaneously may be an effective way to overcome resistance in pts with rel/ref MM. Aim: Orlowski et al reported improved anti-tumor responses when bortezomib (V) was combined with doxil (D) in pts with hematologic malignancies. We investigated clinically, this approach i.e., targeting the MM cell as well as its ME, using a combination of V, D and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Here we report the final results along with survival data of this phase II study. Methods: All pts with rel/ref disease were eligible for this study. V was given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4–6 cycles. SWOG criterion was used to assess response. Low-dose coumadin (1–2 mg po qd) was used for prevention of venous thromboembolism (VTE). Results: Twenty three pts (9M, 14F; median age −57 , range 43–79 yrs; 21MM, 2 WM) have been enrolled. All pts had Stage III disease, median b2M was 4.2 and median number of prior therapies were 5(range 1–6). Prior therapies included stem cell transplant(SCT) in (41%), T (41%), adriamycin(A) (65%) steroids (82%) and velcade (12%). 74% had refractory disease. Seventeen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken off study for non-compliance after 1 cyc. ORR was with 65%(CR+PR) with 23% CR all of whom were IFE negative. The Median Progression Free survival was 10.9 months with an median overall survival of 15.7 months. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. No significant non-hematologic Gr. III/IV toxicity were seen. Despite prior exposure to anthracycle, we did not noted any cardiotoxicity with D.No significant neuropathy was noted. Conclusions: Pt with rel/ref MM usually have aggressive disease with paucity of effective regimens. VDT is an effective salvage regimen. Final results show high response rates with 22% of the patients achieving complete (IFE−) remissions. Responses were noted regardless of type of prior therapy. VDT could be safely given in patients with renal failure/insufficiency. Venous Thromboembolism (VTE) does not appear to be a problem with low dose coumadin prophylaxis. Final results of this phase II study will be presented at the 48 th annual ASH meeting.

Introduction: Lenalidomide (L) is clinically active in pts with CLL. TFR is a common side effect of L, unique to CLL pts and is characterized by tender enlargement of lymph nodes (LN), spleen and/or liver with low-grade fever, rash and/or increase in white blood cell count. Onset is usually with 24 hours of first dose and it is rarely seen after the 1st cycle. The underlying etiology of TFR remains undetermined though clinical presentation is suggestive of an immune activation phenomenon. Diagnosis, management and effective prophylaxis of TFR is crucial for the pt care as it is associated with considerable morbidity and mimics disease progression. We investigated the effectiveness of low-dose prednisone prophylaxis in CLL pts treated with L. Method & Results: Forty five pts (36 male, 9 female), median age 64 years (range 42–75) with rel/ref CLL were enrolled on a phase II clinical trial. Single agent L (max. dose 25mg/day) was given to all pts enrolled. No prophylaxis was given to the first 29 pts (group A). Subsequently 16 pts (group B) were treated with prednisone 20mg PO QD × 5 days followed by 10mg PO QD × 5 days, starting day 1 of treatment. Median age was 64 years (range 42–75) with 36M and 9F. Stage III/IV disease was noted in 64% (n=18) of the pts. Twenty four (83%) pts in group A and 13 (81%) in group B developed TFR with > grade II TFR was seen in 31% and 6%, respectively. Among pts with TFR, 4 achieved complete remission (CR) and had grade > 2 reaction vs. 19 pts with a < partial remission who had a median of grade 1 (range 1–2) TFR. Conclusion: Although the sample size investigated is small, we observed that use of oral prednisone prophylaxis decreased the severity but not the overall incidence of TFR. We therefore recommend that low-dose prednisone be considered for lenalidomide associated TFR in patients with CLL.