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PURPOSE: The role of frailty in affecting survival in myelodysplastic syndromes (MDS) is increasingly recognized. Despite this, a paucity of data exists on the association between frailty and other clinically meaningful outcomes including health care resource utilization and costs of care. METHODS: We linked the Ontario subset of the prospective Canadian MDS registry (including baseline patient/disease characteristics) to population-based health system administrative databases. Baseline frailty was calculated from the 15-item MDS-specific frailty scale (FS-15). Primary outcomes were public health care utilization and 30-day standardized costs of care (2019 Canadian dollars) determined for each phase of disease (initial, continuation, and terminal phases). Negative binomial regression was used to assess the association between frailty and health care costs with Poisson regression to explore predictors of hospitalization. RESULTS: Among 461 patients with complete FS-15 scores, 374 (81.1%) had a hospitalization with a mean length of stay of 10.6 days. Controlling for age, comorbidities, Revised International Prognostic Scoring System, and transfusion dependence, the FS-15 was independently associated with hospitalization during the initial ( P = .02) and continuation ( P = .01) phases but not the terminal disease phase ( P = .09). The mean 30-day standardized cost per patient was $8,499 (median, $6,295; interquartile range, $2,798-$11,996), largely driven by cancer clinic visits and hospitalization. On multivariable analysis, the FS-15 was independently associated with costs of care during the initial disease phase ( P = .02). CONCLUSION: We demonstrate an association between frailty and clinically meaningful outcomes including hospitalization and costs of care in patients with MDS. Our results suggest that baseline frailty may help to inform patients and physicians of expected outcomes.

Background: Observational studies suggest an anti-neoplastic effect associated with statins, metformin, dipeptidyl peptidase-4 inhibitors (DPP4i), while sulfonylureas may have a neutral or detrimental effect. The aim of this study was to determine the impact of these medications in patients with myelodysplastic syndromes (MDS). Methods: A prospective Canadian national registry containing disease and patient-related characteristics enrolled patients with MDS between January 1, 2006 and December 31, 2019. The Ontario subset of the registry was linked to population-based health system administrative databases. The primary outcome was the impact of statin/oral hypoglycemic medication exposure on overall survival (OS). Cumulative medication exposure (in months) was evaluated from 1-year prior to registry enrollment to date of death or end of follow-up (March 31, 2020) as a time-varying covariate. Cox regression analysis controlling for comorbid disease burden (Aggregated Diagnosis Groups; ADG) and sociodemographic factors (age, sex, rurality, income quintile) examined the relationship between medication exposure and OS. Our secondary outcome was leukemia-free survival (LFS), in which cause-specific hazard model was used to evaluate the association between medication exposure and LFS, taking death as the competing event. Results: In total, 533 patients aged >66 years were included (395 lower-risk IPSS, 130 higher-risk IPSS). The median age was 76.0 years (IQR 72.0-81.0), 65.1% were male and 9% had secondary MDS. The mean follow-up was 2.6 years (SD+ 2.4). Starting one year prior to registry enrollment and until the end of follow-up, 49.3% used a statin, 18.9% used metformin, 9.0% used a sulfonylurea and 6.4% used a DPP4i. On univariate analysis, we identified an improved OS in the lower-risk IPSS group using DPP4i (HR 0.98, 95% CI 0.95-1.00, p=0.05), while there was no significant difference in the higher-risk IPSS group for users of DPP4i (HR 1.03, 95% CI 0.99-1.07, p=0.21). In both lower and higher-risk IPSS groups, there was no difference in mortality for statins (HR 1.00, CI 1.00-1.01, p=0.93), metformin (HR 1.00, CI 0.99-1.01, p=0.81) and sulfonylureas (HR 1.00, CI 0.99-1.02, p=0.43). Increased age (p There was no association between exposure to the studied medications and LFS in the lower-risk group: metformin (HR 0.99, 95% CI 0.96-1.02, p=0.32), sulfonylureas (HR 0.99, 95% CI 0.94-1.04, p=0.57) and statins (HR 0.99, 95% CI 0.98-1.01, p=0.41). The impact of DPP4i exposure on LFS could not be assessed in lower risk disease due to infrequent events. There was also no association in the higher-risk IPSS group: DPP4i (HR 1.06, 95% CI 1.00-1.12, p=0.05), metformin (HR 1.02, CI 0.98-1.05, p=0.34), sulfonylureas (HR 1.04, 1.00-1.08, p=0.07) and statins (HR 1.02, 1.00-1.04, p=0.12). On multivariable analysis in the lower-risk IPSS group, no associations were identified between the use of medications of interest and all-cause mortality: DPP4i (HR 0.98, 95% CI 0.95-1.00, p=0.06), metformin (HR 1.00, 95% CI 0.99-1.01, p=0.99), sulfonylurea (HR 1.00, 95% CI 0.99-1.02, p=0.65) and statins (HR 1.00, 95% CI 0.99-1.00, p=0.56). In those with known cause of death, the main cause of death amongst DPP4i users was infection (35.7%) followed by acute myeloid leukemia (AML) (21.4%) and cardiac disease (14.3%), while the main cause of death in patients not on DPP4i was progressive MDS (23.2%) followed by AML (22.5%) and infections (22.1%). Conclusions: DPP4i may confer a survival benefit in lower-risk but not higher-risk MDS that cannot be explained by a reduction in cardiovascular deaths. Metformin, sulfonylureas and statins showed no impact on OS and LFS in lower and higher-risk groups. Improved bone marrow function through exosome inhibition and increased granulocyte-macrophage colony stimulating activity is the suggested mechanism for the potential survival benefit with DPP4i in lower-risk IPSS patients. This represents the first study evaluating the impact of oral hypoglycemic mediations and statins in a large cohort of patients with MDS. Further prospective studies are required to further evaluate the effects of DPP4i in MDS. Disclosures Leber: AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TaiHo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Khalaf: Pfizer: Honoraria; Novartis: Honoraria; Paladin: Honoraria. Sabloff: TaiHo: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Jaxx: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Yee: Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Research Funding; Janssen: Research Funding; Jazz: Research Funding; MedImmune: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Research Funding; Tolero: Research Funding; AbbVie: Honoraria; Bristol-Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; Paladin: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; TaiHo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; F. Hoffmann La Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Forma Therapeutics: Research Funding. Buckstein: Celgene: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; TAIHO: Research Funding; Otsuka: Research Funding.

The optimal hemoglobin (HgB) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. We conducted a randomized multi-center study of two transfusion algorithms (liberal, to maintain Hgb 110-120 g/L, versus restrictive, 85-105 g/L) and combined our findings from RBC-ENHANCE with those of REDDS a previously published study of similar design. Primary objectives were measures of compliance to transfusion thresholds and the achievement of a 15 g/L difference in pre-transfusion Hgb. Secondary outcomes included measures of QOL, iron studies and safety. 66 patients were randomized between February 2015-2020, 33 to each arm in 15 international participating sites. The compliance was 58% and 81% in the restrictive and liberal arms respectively and the mean pre-transfusion Hgb thresholds for restrictive and liberal arms were 85.9 (SD 9) and 98.8 g/L (SD 9). Patients in the liberal arms experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) extra units of blood during the 12-week study. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important differences in the liberal arm. Further data are needed to establish the feasibility of liberal transfusion policies in MDS outpatients. Trial Registration: REDDS: ISRCTN26088319 RBC-ENHANCE: NCT 02099669

Patients with lower-risk (LR) myelodysplastic syndromes (MDS) with ring sideroblasts (RS) have better prognosis than those without RS, but how they fare over time is not fully understood. This study's objective was to assess the natural history of LR MDS with RS ≥5% using MDS-CAN registry individual data. Kaplan-Meier estimates and generalized linear mixed models were used to describe time-to-event outcomes and continuous outcomes, respectively. One hundred and thirty-eight patients were enrolled; median times from diagnosis to enrollment and follow-up were 6.6 and 39.6 months, respectively. Within 5 years of enrollment, 65% of patients had ≥1 red blood cell transfusion dependence episode. Within 5 years of diagnosis, 59% developed iron overload, 38% received iron chelation therapy, 14% progressed to acute myeloid leukemia, and 42% died. Patients exhibited inferior health-related quality of life trends. These first real-world data in LR MDS-RS in Canada indicate a high level of morbidity and mortality over a 5-year period.

Background:Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancers, but their association with frailty and how to manage them optimally remain unclear.Patients and Methods:From 2015 to 2019, patients aged ≥75 years presenting for initial oncology consult underwent screening geriatric assessment. Patients were determined to be robust, prefrail, or frail via deficit accumulation and phenotypic approaches. We quantified each patient’s total number of medications and PIMs using the Anticholinergic Risk Scale (ARS) and a scale we generated using the NCCN Medications of Concern called theGeriatric Oncology Potentially Inappropriate Medications(GO-PIM) scale. We assessed cross-sectional associations of PIMs with frailty in multivariable regression models adjusting for age, gender, and comorbidity.Results:Of 785 patients assessed, 603 (77%) were taking ≥5 medications and 421 (54%) were taking ≥8 medications; 201 (25%) were taking at least 1 PIM based on the ARS and 343 (44%) at least 1 PIM based on the GO-PIM scale. Among the 468 (60%) patients on active cancer treatment, taking ≥8 medications was associated with frailty (adjusted odds ratio [aOR], 2.82; 95% CI, 1.92–4.17). With each additional medication, the odds of being prefrail or frail increased 8% (aOR, 1.08; 95% CI, 1.04–1.12). With each 1-point increase on the ARS, the odds of being prefrail or frail increased 19% (aOR, 1.19; 95% CI, 1.03–1.39); with each additional PIM based on the GO-PIM scale, the odds increased 65% (aOR, 1.65; 95% CI, 1.34–2.04).Conclusions:Polypharmacy and PIMs are prevalent among older patients with blood cancers; taking ≥8 medications is strongly associated with frailty. These data suggest careful medication reconciliation for this population may be helpful, and deprescribing when possible is high-yield, especially for PIMs on the GO-PIM scale.

Introduction: Previous studies have demonstrated that frailty is associated with mortality among patients with non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL). However, no studies have examined frailty in an unselected population-based sample of patients with DLBCL, nor have data on health care utilization been considered as a potential mediator of this relationship. Objective: To determine whether frailty is associated with one-year survival in an unselected population of patients with DLBCL, and examine whether its impact is mediated by health care utilization during chemotherapy treatment. Methods: A retrospective cohort study was conducted using population-based health care data in Ontario, Canada. Patients >65 years diagnosed with DLBCL or transformed follicular lymphoma between January 2006 and December 2017 and receiving first-line chemo-immunotherapy were included. Frailty was defined by modifying a previously validated score developed for use with population-based data in Ontario, comprising 30 multidimensional variables (McIsaac, Ann Surg. 2019;270(1):102-108). Patients were categorized as "frail" (score >0.21) vs. "non-frail" (score ≤0.21). Covariates included age, number of comorbidities based on the Johns Hopkins Aggregated Diagnosis Groups (ADGs), and health care utilization during chemotherapy (defined as emergency department (ED) visit or inpatient hospitalization not resulting in death during treatment, and analysed as a time-varying covariate). Cox regression was performed to examine the association between frailty and one-year mortality (primary outcome). Secondary outcomes included health care utilization, chemo-immunotherapy exposure, and cause of death. Results: 5,527 patients were included in the study. 5,216 patients (94%) had de novo DLBCL, and 311 (6%) of patients had transformed follicular lymphoma. The median age was 75 years (IQR 70-80), and 48% (N=2672) were female (Table 1). 2,699 (49%) of patients were classified as frail (Table 2). Frail patients tended to be older (median age 76 (IQR 71-81) vs. 74 years (IQR 70-79)). The difference in mortality between frail and non-frail patients was most pronounced in the initial year following start of treatment (Figure 1a). Within 90 days of first-line rituximab, 14% (N=370) of frail vs. 7% (N=185) of non-frail patients had died (p The relationship between frailty and survival remained consistent when measured in quartiles (HR 1.6 (95% CI 1.3-1.9) for Q2, 2.0 (95% CI 1.7-2.4) for Q3, 2.7 (95% CI 2.3-3.2) for Q4, p Conclusion: Frailty is significantly associated with one-year mortality in patients with newly diagnosed DLBCL, even after adjusting for age, comorbidities, and health care utilization. Frailty appears to be associated with poor tolerability of chemotherapy and a higher likelihood for requiring acute hospital-based care, and future analyses will explore whether this is related to patients suffering increased treatment-related toxicity. Future analyses of these data will also address whether frail patients who die within one-year of first-line treatment have different clinical characteristics compared to frail patients who survive beyond one year. Future prospective studies may help clinicians understand whether any frailty-related variables are modifiable and the role of alternative treatment strategies for vulnerable patients. Disclosures Prica: astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria.

Background: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. Methods: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. Results: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70–80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6–2.0; PPConclusions: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.

For patients with blood cancers, comorbid mental health disorders at diagnosis likely affect the entire disease trajectory, as they can interfere with disease information processing, lead to poor coping, and even cause delays in care. We aimed to characterize the prevalence of depression and anxiety in patients with blood cancers. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients ≥67 years old diagnosed with lymphoma, myeloma, leukemia, or myelodysplastic syndromes between 2000 and 2015. We determined the prevalence of precancer depression and anxiety and cancer-associated (CA) depression and anxiety using claims data. We identified factors associated with CA-depression and CA-anxiety in multivariate analyses. Among 75 691 patients, 18.6% had at least 1 diagnosis of depression or anxiety. Of the total cohort, 13.7% had precancer depression and/or precancer anxiety, while 4.9% had CA-depression or CA-anxiety. Compared with patients without precancer anxiety, those with precancer anxiety were more likely to have subsequent claims for CA-depression (odds ratio [OR] 2.98; 95% CI 2.61-3.41). Other factors associated with a higher risk of CA- depression included female sex, nonmarried status, higher comorbidity, and myeloma diagnosis. Patients with precancer depression were significantly more likely to have subsequent claims for CA-anxiety compared with patients without precancer depression (OR 3.01; 95% CI 2.63-3.44). Female sex and myeloma diagnosis were also associated with CA-anxiety. In this large cohort of older patients with newly diagnosed blood cancers, almost 1 in 5 suffered from depression or anxiety, highlighting a critical need for systematic mental health screening and management for this population.

Background: Frailty is associated with poor tolerance to chemotherapy and mortality. While recent evidence suggests measures of frailty such as gait speed predict survival in older patients with hematologic malignancies such as lymphoma (Liu, Blood, 2019), its predictive ability has not been compared to disease-based prognostic risk scores. Methods: From February 2015 to April 2019, all patients aged 75 years and older who presented for initial consultation for at the Dana-Farber Cancer Institute for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Waldenstrom macroglobulinemia (WM) were approached for a screening frailty evaluation by a trained research assistant. As part of the evaluation, 4-meter gait speed was assessed (at normal pace with non-ambulatory patients recorded as having a speed of zero). Disease-specific prognostic scores were obtained retrospectively, including the International Prognostic Index (IPI) for DLBCL, the Follicular Lymphoma International Prognostic Index (FLIPI) for FL, and the International Prognostic Scoring System for Waldenstrom Macroglobulinemia (ISSWM). Univariate and multivariable Cox proportional hazard models were used to determine predictors of overall survival (OS; from date of screening geriatric assessment) including gait speed and disease-specific scores. Those with incomplete risk data excluded from disease-specific analyses. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: A total of 145 patients were included, 59 with DLBCL, 30 with FL, 56 with WM. Median age was 79 (IQR 77 to 82) and 42.1% were female. For the overall cohort, mean gait speed was 0.78 (±0.27). Risk score distribution and disease-specific gait speed are presented in the table. With a median follow-up of 20.9 months (IQR 10.2 to 34.5), median OS was 14.4 months for DLBCL, 17.2 months for FL and 32.0 months for WM. Disease-specific prognostic scores were not predictive of survival for DLBCL (p = 0.76) or FL (p = 0.22) but were for WM (p = 0.04). Overall, faster gait speed was significantly predictive of OS (HR 0.10, 95% CI 0.03 to 0.32, p < 0.0001) for all three lymphomas combined, which would mean an HR of 0.56 for an increase of 0.25 m/s of gait speed. In disease-specific analyses, faster gait speed was predictive of survival for DLBCL (HR 0.10, 95% CI 0.02 to 0.46, p = 0.003) and WM (HR 0.11, 95% CI 0.01 to 0.83, P = 0.03) but not for FL (P = 0.26). In DLBCL, gait speed explained significant variability in OS (R2 = 22.95%) compared with IPI score (R2 = 1.87%; p = 0.005) whereas it did not for WM compared with IPSSWM (R2 = 10.22% vs. 5.58%, p = 0.11) or FL compared with the FLIPI (R2= 12.21% vs. 8.10%, p = 0.35). Conclusion: Gait speed may help to further refine the prediction of outcomes in patients with aggressive lymphomas beyond standard prognostic scores but may have less of an effect for indolent lymphomas. These data suggest that gait speed should be incorporated into the standard assessment of patients with aggressive lymphomas. Table Disclosures Buckstein: Takeda: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Soiffer:Mana therapeutic: Consultancy; Kiadis: Other: supervisory board; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Cugene: Consultancy; Jazz: Consultancy.

Background: The incorporation of patient-reported outcomes with traditional disease risk classification, was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). A recently reported model, FA-IPSS(h), found that patients' reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), among higher-risk IPSS population, further stratifies them into distinct sub-groups with different survival outcomes (Efficace et al, 2018). Compared to the IPSS, the revised IPSS (IPSS-R) is more refined in prognostic assessment and an IPSS-R score of > 3.5 may identify higher risk disease (Pfeilstocker et al, 2016). The Edmonton Symptom Self Assessment Scale (ESAS) Global Fatigue Scale (GFS), is a single-item fatigue rating scale (0-10, with 10 being the highest degree), which has been previously recommended by the National Comprehensive Cancer Network to screen for fatigue in all cancer populations. Aims: (1) to validate the FA-IPSS(h), among the Canadian MDS registry (2) investigate whether a modified index, integrating higher risk by IPSS-R with patient reported fatigue according to the GFS, is able to identify individual subgroups with divergent overall survival (OS). Methods: All adult patients diagnosed with MDS with an IPSS-R score >3.5 within 6 months before the date of registration were eligible for this analysis. Fatigue was assessed both by the QLQ-C30 questionnaire and the GFS. Frailty was assessed by the Canadian Study of Health and Aging (CSHA) 9 point Rockwood clinical frailty scale. Survival was calculated using standard Kaplan-Meier analysis. Results: This analysis included 331 patients. Median age was 73 years (range, 30-98 years), 65.7% were male, median blast % was 6% (range, 0-30), median IPSS-R score was 5.2 (range, 3.5-10) and 55% had high and intermediate-2 (Int-2) IPSS risk, 68% had high and very high IPSS-R risk disease, 66% were exposed to a hypomethylating agent. Median fatigue scores increased with Rockwood frailty scores. The median QLQ-C30 fatigue score was 33 (interquartile range (IQR), 22-55.6) and 4 (IQR, 2-6) by the GFS with 59% recording high fatigue (>4). At a median follow-up of 17 months (IQR, 9-30 months), 233 deaths were observed. The actuarial median OS was 19.3 months (95% CI, 16.5-21.7). We applied the FA-IPSS(h) using QLQ-C30 fatigue cutoffs of 45 (figure 1a) and found a significant difference in OS (p3.5 + Low Fatigue (3.5 + High Fatigue (≥45) (n=96). We found a significant difference in OS between these 2 groups, median OS 19.5 months (95% CI, 17.2-24.3) in group A versus 15.2 months (95% CI, 11.9-22.0) in group B (p=0.02) (figure 1b). We found similar results with these refinements, using the QLQ-C30 cutoff of 33 (the median in our patient population) (p4), was able to distinguish OS using the IPSS (p3.5 (p=0.005) (figure 1d). Conclusions: We were able to externally validate the FA-IPSS (h) using a threshold QLQ-C30 fatigue score of 45, as originally described and 33 (Canadian median), using both the IPSS and IPSS-R (score >3.5) classifications to define higher risk MDS. The easier to deploy ESAS GFS score of >4 further discriminates survival using the IPSS and IPSS-R. This emphasizes the power of self-reported fatigue at refining OS predictions in higher risk MDS and further bolsters the importance of considering patient related outcomes in global assessments. Disclosures Geddes: Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Keating:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Servier: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Taiho: Membership on an entity's Board of Directors or advisory committees. Leber:Lundbeck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda/Palladin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Treadwell: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Leitch:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Exjade: Speakers Bureau. Shamy:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Storring:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nevill:Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Delage:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Elemary:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chodirker:Hoffman Laroche: Honoraria. Buckstein:Novartis: Honoraria; Celgene: Research Funding; Takeda: Research Funding; Celgene: Honoraria; Astex: Honoraria.

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.

The incorporation of patient-reported outcomes with traditional disease risk classification was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). In the present Canadian MDS registry analysis, we validate a recently reported prognostic model, the Fatigue-International Prognostic Scoring System among higher-risk patients [FA-IPSS(h)], which incorporates patients' reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), with a threshold of ≥45 points, in higher IPSS score, stratifying them into distinct subgroups with different survival outcomes. We further validated this concept, using the Revised IPSS >3·5 as cut-off for the definition of higher-risk MDS, and patients' reported fatigue according to Edmonton Symptom Self-Assessment Scale (ESAS) Global Fatigue Scale (GFS), a single-item fatigue rating scale, which is easier to deploy. This emphasises the power of self-reported fatigue at refining overall survival predictions in higher-risk MDS and further bolsters the importance of considering patient-related outcomes in global assessments.

PURPOSE: Azacitidine (AZA) is a standard of care for higher-risk myelodysplastic syndrome (MDS)/low blast–count acute myeloid leukemia (AML). Despite this, there is a paucity of data on the real-world health care resource utilization costs of AZA in this population. METHODS: We linked the Ontario AZA MDS registry—higher-risk MDS/low blast–count AML—to population-based health system administrative databases. Patients were observed for 24 months after first AZA and censored at the earliest of 90 days after last AZA, date of death, time of AML induction/stem-cell transplantation, or March 31, 2016. Costs (2015 Canadian dollars) were expressed as standardized mean and median 28-day costs. Univariable quantile regression was used to explore the association of baseline patient and disease characteristics and median cost. Multivariable quantile regression was used to explore predictors of median costs. RESULTS: Among 877 patients in the registry, mean standardized 28-day cost per patient was $17,638 (median, $15,272; interquartile range [IQR], $11,869-$19,580) and $13,450 (median, $11,043; IQR, $7,981-$14,882) excluding the cost of AZA. Major nondrug drivers of cost were cancer clinic visits and inpatient care (mean standardized 28-day cost, $4,631; median, $1,558; IQR, $238-$4,961). Transfusion dependence at AZA initiation ( P = .001) and greater comorbid disease burden ( P = .009) were independently associated with increased cost. CONCLUSION: Our cohort of patients with uniformly higher-risk MDS/low blast–count AML treated with AZA demonstrates substantial costs of care above and beyond the cost of AZA alone. These results provide insight into the costs of AZA in the real world with implications for resource allocation.

Background: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. Results: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8–13), and median DTI was 37 days (IQR, 22–61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4–2.8 years). Shorter DTI was a significant predictor of mortality (PConclusions: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

Health resource utilization (HRU) and associated factors of high cost are not well understood in myeloproliferative neoplasms (MPNs). In this population-based, retrospective matched-cohort study, we used administrative health databases of Ontario, Canada to measure treatment costs and HRU for patients with MPN from 2004 to 2016 and compared them to matched controls. In 7130 patients with MPN [essential thrombocythemia (ET) = 3481; polycythemia vera (PV) = 2618; myelofibrosis (MF) = 1031], the mean annualized treatment costs were $16,646 for ET (controls, $7070); $16,360 for PV (controls, $7293); and $25,863 for MF (controls, $7386). Out of the total costs, the largest expenditure was on acute hospital care (ET: 57%, PV: 57%, MF: 66%). Older age (≥65), male gender, patients not seen by a specialist, and greater comorbidity burden were independent predictors of higher costs (

Despite the adoption of azacitidine (AZA) in higher-risk MDS/low-blast count AML, limited 'real-world' data on resource utilization and toxicity exist. We linked the Ontario AZA-MDS registry to population-based administrative databases. Among 877 patients in the registry, 705 (80.4%) had at least one emergency department (ED) visit, 290 (33.1%) had an ED visit during their first cycle and 680 patients (77.5%) had at least one hospitalization (mean length 17.7 days, 95% CI 16.3-19.1). Older age, rurality, non-response to AZA, transfusion dependence, IPSS score, and greater comorbidity were independent predictors of increased ED visits; while greater comorbidity, non-response to AZA, and transfusion dependence were associated with longer hospitalization. When restricted to receiving ≥3 cycles, hospitalization during the first cycle was associated with increased risk of death. Our analysis of 'real-world' patients treated with AZA demonstrates significant healthcare utilization and increased risk of death for patients hospitalized during their first cycle. These results will inform patients/providers about 'real-world' toxicities of AZA.

Preclinical data suggests anti-lymphoma potential for statins, metformin and cyclooxygenase-2 (COX-2) inhibitors. We performed a retrospective population-based study of all adults aged ≥66 years diagnosed with diffuse large B-cell lymphoma (DLBCL) or transformed lymphoma treated with a rituximab containing regimen, between 2005 and 2015 in Ontario, Canada. Using administrative databases, we assessed the impact of medication exposures, prior to chemo-immunotherapy, on lymphoma survival. Cox regression analyses, controlling for sociodemographic factors and comorbidities, examined the relationship between medication exposure and survival. In total, 4913 patients were treated with curative intent (median age 75 years, 51% male) and 52·2% died at a median of 1 year from treatment initiation (67% due to DLBCL). In the year prior to commencing treatment, 45·7% received statins, 16·3% metformin, and 25·0% a COX-2 inhibitor. Adjusting for confounders, exposure to statin and COX-2 inhibitors prior to chemo-immunotherapy independently conferred a survival advantage: statin exposure for 30 days (hazard ratio [HR] 0·97, 95% confidence interval [CI] 0·96-0·98), 180 days (HR 0·84, 95% CI 0·80-0·89) and 365 days (HR 0·71, 95% CI 0·63-0·79) and COX-2 inhibitor exposure for 30 days (HR 0·95, 95% CI 0·95-0·98), 180 days (HR 0·76, 95% CI 0·66-0·86) and 365 days (HR 0·57, 95% CI 0·43-0·74). Metformin had no significant impact. This population-based study found a dose-related survival benefit of exposure to statins and COX-2 inhibitors prior to chemo-immunotherapy for newly diagnosed DLBCL.

Background. Polypharmacy and potentially inappropriate medications (PIMs) are common among older adults with blood cancer and can lead to adverse effects and poor outcomes. Polypharmacy is commonly defined as taking ≥5 or ≥8 medications, depending on the population. PIMs can cause adverse side effects for certain patients, e.g. diphenhydramine and benzodiazepines. We sought to define the prevalence of polypharmacy and PIMs in older adults with blood cancers, and to examine the association between both with cognitive impairment and frailty in this population. Methods. From February 2015 to November 2019, all transplant-ineligible patients ages 75 and older who presented for initial consultation for hematologic malignancy at the Dana-Farber Cancer Institute (Boston, MA) were approached by a research assistant (RA) for a 15-minute screening geriatric assessment. The RA assessed 42 aging-related health deficits using patient-reported and objective performance measures spanning the domains of function, cognition, comorbidity, and mobility. Patients were determined to be frail, pre-frail or robust via two approaches: deficit accumulation approach (Rockwood, JGMedSci 2007) and phenotypic approach (Fried, JGMedSci 2001). Cognition was measured using the delayed recall section of the Montreal Cognitive Assessment (MoCA; Nasreddine, JAGS 2005) and Clock-In-Box test (CIB; Chester, Am J Med 2011). In addition, we collected data via electronic medical record review of all prescribed and over-the-counter medications patients were taking at the time of initial consultation. These data were reconciled and reviewed for quality by two board-certified geriatricians. The geriatricians identified 2 types of PIMs: anticholinergic PIMs per the Anticholinergic Risk Scale (Rudolph, Arch Intern Med 2008) and cancer-specific PIMs per the National Cancer Care Network Medications of Concern (NCCN Older Adult Oncology 2020). For patients recommended for active cancer treatment, the association between polypharmacy and PIMs with frailty was assessed using ordinal logistic regression. The association between polypharmacy and PIMs with cognitive impairment (by MoCA delayed recall and CIB) was assessed using logistic regression. All models controlled for age, gender, and comorbidity (via Charlson Comorbidity Index). Results. In this patient cohort (N=785), 286 (36%) were female with 240 (30%) in the leukemia disease group, 272 (35%) lymphoma and 273 (35%) multiple myeloma. 603 (77%) patients had polypharmacy (≥5 medications) and 421 (54%) were taking ≥8 medications. 201 (25%) patients were taking at least one PIM based on the Anticholinergic Risk Scale (Rudolph) and 343 (44%) based on the NCCN guidelines. Overall, 131 (17%) were frail, 457 (58%) pre-frail and 197 (25%) robust. 541 (69%) patients had Charlson Co-morbidity Index ≥3; 111 (14%) patients had "probable" cognitive impairment by MoCA Delayed Recall and 147 (19%) had "probable" cognitive impairment by CIB. In the 468 (60%) patients on active cancer treatment, there was an association of frailty with polypharmacy defined by a cutoff of ≥8 (adjusted odds ratio [aOR]=2.82, 95% confidence interval [CI] 1.92-4.17), but not ≥5 medications (aOR=1.42, 95% CI 0.91-2.22; Table 1). With each additional medication on a patient's medication list, their odds of being more frail increased by 8% (aOR=1.08, 95% CI 1.04-1.12). With each one-point increase on the Anticholinergic Risk Scale, odds of being more frail increased by 19% (aOR=1.19, 95% CI 1.03-1.39). With each additional PIM based on NCCN guidelines, odds of being more frail increased by 65% (aOR=1.65, 95% CI 1.34-2.04). Polypharmacy and PIMs were not associated with cognitive impairment by either MoCA Delayed Recall or CIB. Conclusion. Polypharmacy and PIMs are prevalent among older patients with blood cancers and are strongly associated with frailty but not cognitive impairment, independent of comorbidity. Increasing number of anticholinergic and especially cancer-specific PIMs have a stronger association with frailty compared to increasing number of medications in general. Our findings highlight that the types of medications contributing to polypharmacy may be more important than number of total medications. This suggests the need for streamlined ways of identifying specific PIMs in practice to deprescribe medications that may be associated with cumulative harm in older adults with cancer. Figure 1 Figure 1. Disclosures Stone: Aprea: Consultancy; Boston Pharmaceuticals: Consultancy; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; OncoNova: Consultancy; Syndax: Membership on an entity's Board of Directors or advisory committees; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy; Macrogenics: Consultancy; Novartis: Consultancy, Research Funding; Glaxo Smith Kline: Consultancy; Innate: Consultancy; Janssen: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Consultancy; Gemoab: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Research Funding; Actinium: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Syros: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy. Soiffer: Rheos Therapeutics, USA: Consultancy; Kiadis, Netherlands: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics, USA: Other: Data Safety Monitoring Board; Precision Biosciences, USA: Consultancy; Jazz Pharmaceuticals, USA: Consultancy; Takeda: Consultancy; Jasper: Consultancy; Gilead, USA: Other: Career Development Award Committee; NMPD - Be the Match, USA: Membership on an entity's Board of Directors or advisory committees.

Introduction: While health disparities in diffuse large B-cell lymphoma (DLBCL) have been previously noted, literature systematically describing the impact of social determinants of health (SDOH) on DLBCL overall survival (OS) is sparse. Furthermore, existing data largely examine SDOH of health in isolation, not accounting for key covariates or disease-related variables. Marginalization, which accounts for various SDOH, is a process of systemic discrimination and exclusion. Given the paucity of literature to date, we examined how marginalization influences DLBCL OS in the Canadian setting. The objectives of this study were: 1) To describe the impact of marginalization on DLBCL OS and 2) To identify which dimensions of marginalization, if any, impacted OS. Methods: We conducted a population-based retrospective cohort study of adult patients with newly diagnosed DLBCL in Ontario between January 1, 2005 to December 31, 2017 receiving a rituximab-containing chemotherapy regimen for curative intent, followed until March 1, 2020. Our primary exposure of interest was the Ontario Marginalization Index (ON-Marg), an administrative database tool which combines demographic indicators into four distinct marginalization dimensions: residential instability (% renters and % living alone), material deprivation (% low income and % lone parent families), dependency (% seniors and % employment), and ethnic concentration (% recent immigrants and % visible minority). Our primary outcome was 2-year OS, defined as time from the date of first rituximab-based treatment to date of death or completion of follow-up. Survival curves were generated using Kaplan-Meier methods, and Cox regression analyses were used to identify covariates that were independently associated with OS. Our final model adjusted for age (as increments of 10 years), sex, and comorbidity burden as measured by aggregate diagnostic groups (ADGs). Results: A total of 10,344 patients were diagnosed with DLBCL and treated with a rituximab-containing regimen in Ontario between January 1, 2005 and December 31, 2017. The median age was 67 (IQR, 55-75) and 46% were female. Of patients who had staging data (49%), 54% were advanced stage at diagnosis, and the median number of cycles of chemoimmunotherapy received was 6 (4-6). Median number of ADGs was 10 (8-12), indicating a moderate-to-high burden of comorbidities within this cohort, and 13% of patients resided in a rural area. Cohort characteristics and mortality rates per ON-Marg quintile (Q5 = most marginalized) are provided in Table 1. Overall, group characteristics were evenly distributed, except that the most marginalized group had a higher proportion of patients residing in urban settings and nearer to treatment hospitals. Two-year overall survival was 73.2%. After controlling for relevant confounders, material deprivation (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02 - 1.10, p=0.003) and ethnic concentration (HR 1.05, 95% CI 1.01 - 1.09, p=0.013) contributed to increased risk of all-cause mortality. Residential instability and dependency had no significant effect. Increasing age (HR 1.29, 95% CI 1.25 - 1.33, p Discussion: To our knowledge, no study has examined the impact of marginalization and collective SDOH on DLBCL outcomes. We found that increased material deprivation and ethnic concentration conferred increased mortality. While Canada's largely single-payer system and previously documented healthy immigrant effect may have been expected to attenuate effects of income and immigration, our study suggests otherwise. Possible explanations may include barriers to healthcare access for patient subsets, who may have less support for treatment. Structural factors such as systemic racism, health literacy, and caregiver burden must also be taken into account. These factors require further evaluation to inform targeted interventions and establish support for increased access to timely care amongst this patient population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction While prior studies suggest that mental health complications are underdiagnosed and undertreated in patients with cancer, a paucity of data exists for patients with diffuse large B-cell lymphoma (DLBCL). Indeed, mental illness can impact the success of potentially curative treatment for DLBCL including delays in treatment initiation, poor chemotherapy compliance, and suboptimal rates of completion. Accordingly, we aimed to examine the risk of incident mental health events following DLBCL diagnosis, and the association of mental health conditions with overall survival (OS). Methods We conducted a population-based observational study using linked administrative healthcare databases from Ontario, Canada. All Ontario residents aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2017 were identified and followed from the date of first rituximab until March 1, 2020. The primary outcome was any incident mental health event (emergency department visit, hospitalization, or outpatient visit for mood disturbance including depression and anxiety, psychotic disorder, or substance-related disorder). Patients with a DLBCL diagnosis without pre-existing mental health comorbidity in the 2-years prior to start of rituximab were matched to mental health condition- and cancer-free controls in a 1:4 ratio based on birth year and sex. The cumulative incidence function was used to estimate incidence of mental health events while accounting for the competing risk of death, and differences were compared using Gray's K-sample test. A cause-specific Cox regression model was used to estimate mental health events up to two-years following rituximab initiation, while controlling for relevant covariates (sex, age modeled in 10-year interval increments, rural vs. urban residence, income quintile, and quartile of sum of aggregated diagnosis groups (ADGs) as a measure of comorbid disease burden (mental health and cancer diagnoses excluded). The secondary outcome was the association of mental health conditions on OS for all identified DLBCL patients, evaluated using Cox regression (with mental health event as time-varying variable). Results We identified 10,299 patients diagnosed with DLBCL and treated with a rituximab-containing regimen in Ontario, with median age 67 years (IQR 56-76), 45.9% female, median ADG score of 9 (IQR 6-11), and median of 6 cycles of rituximab received (IQR 4-6). For patients with available stage data (49.2% of cohort), 34.6% had stage IV at diagnosis. When compared to birth year- and sex-matched controls (n=29,620), DLBCL cases (n=7,405) had a greater comorbidity burden (p Conclusions In this large population-based study, patients with DLBCL were found to have a significantly higher risk of incident mental health events compared to controls. Moreover, the presence of a mental health condition was associated with worse survival outcomes. These data suggest that patients with DLBCL, particularly those with pre-existing mental health condition(s), would benefit from routine mental health assessment and management during follow-up, not only for mental health itself but also potentially to improve survival. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

Intro: Iron overload (IO) reflected by elevated serum ferritins is associated with increased mortality in patients with myelodysplastic syndromes (MDS) with a threshold effect seen above 1000 ug/ml (Malcovati, JCO 2005). Ferritin is elevated due to transfusions, inflammation and ineffective erythropoiesis but is an imperfect metric of true iron overload. Elevated levels of oxidatively damaging non-transferrin bound iron (NTBI) and labile plasma iron (LBI) are not easily measured but correlate with transferrin saturation (TSAT) >70% and >80% respectively (de Swart, Haematological 2018). The relationship of TSAT with ferritin and MDS-related clinical outcomes has not been well-characterized. Objectives: We aimed to describe temporal trends in TSAT according to transfusion dependence and to determine if elevated TSAT correlates with ferritin levels, and/or predicts for clinical outcomes such as survival, infectious death and cardiac death in patients with MDS. Methods: Adult patients enrolled in the Canadian national MDS registry over 11.5 years and 15 centers were evaluated retrospectively. Mean, median and ranges for ferritin and TSAT were calculated at six (+/- 3) month intervals. General linear mixed model analysis with repeated measures per subject was used to evaluate changes in ferritin and TSAT over time. Transfusion density (TD) was calculated at landmark year 1 and 2 and was defined as the total number of units transfused/months elapsed since commencing transfusion dependence, with TD-low and TD-high defined as above or below median. Log-rank tests were used to detect survival differences among three transfusion groups (transfusion independent [TI], TD-low and TD-high), among three TSAT groups (TSAT 80% at enrolment), and among three ferritin groups (≤500ug/mL, 501-1000ug/mL and >1000ug/mL at enrolment). Results: A total of 718 patients from the MDS-CAN registry were included in the analysis. Patient characteristics including demographics, clinical and laboratory characteristics are summarized in Table 1. With a median follow up of 2.1 years, actuarial OS was 2.4 years. 17% developed AML and 61% of patients have died. AML, progressive disease, infection, cardiac causes, bleeding accounted for 26%, 20%, 19%, 9.6% and 6.34% of known causes of death respectively. 56% experienced infections (median 2/patient), 7% experienced a cardiac event and 43% were hospitalized at least once. Ferritin and TSAT were moderately correlated over time (r=0.63, p < 0.0001) (Figure 1A) with only 39% of all ferritins >1000ug/mL associating with a TSAT of >80%. The relationship between the 2337 serum ferritins (recorded over 42 months) and TSAT is shown in Figure 1B. Among all patients, ferritin significantly increased from enrolment up to 42 months (p Conclusion: Among a cohort of predominantly low-intermediate risk MDS patients, TSAT correlated only moderately with serum ferritins. TD patients, and in particular high transfusion-burden TD patients have inferior clinical outcomes compared to TI or low-transfusion burden TD patients. Further analyses to probe these relationships are ongoing including the effect of TSAT and iron chelation therapy on infectious deaths, and a multivariate analysis adjusting for other covariates. Disclosures Geddes: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Keating:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Taiho: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Leber:Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Treadwell: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda/Palladin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lundbeck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shamy:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Storring:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nevill:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria. Delage:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Elemary:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chodirker:Hoffman Laroche: Honoraria. Leitch:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Exjade: Speakers Bureau. Buckstein:Astex: Honoraria; Celgene: Honoraria; Takeda: Research Funding; Celgene: Research Funding; Novartis: Honoraria.

The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles. The actuarial median survival was 11·6 months [95% confidence interval (CI) 10·7-12·4) for the entire cohort and 18·0 months (landmark analysis; 95% CI 16·6-19·1 months) for those receiving at least 4 cycles. There was no difference in overall survival (OS) between the 3 dosing schedules (P = 0·87). In our large 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML, we demonstrated a lower than expected OS. Reassuringly, survival did not differ by dosing schedules. The OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realised. This represents the largest 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML.

Background: Myeloproliferative neoplasms (MPNs) are chronic myeloid malignancies with markedly heterogeneous disease course, and are associated with underlying inflammatory states that promote development of thrombotic events and acquisition of comorbidities. There is poor understanding of health care resource utilization (HRU) and cost of treatment in patients with MPNs. Objectives:To estimate and compare the HRU and cost of treatment for MPN patients (Essential Thrombocythemia, ET; Polycythemia Vera, PV; and Myelofibrosis, MF) with matched controls, and investigate the impact of patient characteristics and health service factors on the cost of treatment. Study design: Retrospective, population-based, matched-cohort study, using provincial health databases of Ontario's single payer universal health system. Study population: Cases were individuals in the Ontario Cancer Registry, diagnosed with MPN (Total n= 7130; ET, n=3481; PV, n=2618; MF, n=1031), from 2004 to 2016. Controls were individuals in the general population of Ontario, without a diagnosis of MPN. Each case was matched with four controls on age, sex, geographical location, and neighborhood income quintile. Baseline parameters including thrombosis and other comorbidities were collected during two-years prior to the date of MPN diagnosis. The baseline comorbid disease burden was measured using the Aggregated Diagnostic Group (ADG) score with a larger number of ADGs representing a greater comorbid disease burden (https://www.johnshopkinssolutions.com/wp-content/uploads/2014/04/ACG-White-Paper-Applications-Dec-2012.pdf). Main outcome measures:For each case and its controls, direct medical costs were obtained by costing all health care-related resources and expressed as mean per person year costs ((2018 Canadian Dollars, $1 CDN = $0.76 USD) to adjust for variable length of follow-up. Linear regression analysis was performed to assess the impact of baseline factors on the cost of treatment for MPN and represented as rate ratios (95% CI). Results:The mean duration of follow-up in years (cases vs controls) was 3.9 vs 4.3 for ET; 3.9 vs 4.2 for PV and 3.2 vs 4.9 for MF. The total follow-up duration was 27449 person years for all MPN cases, and 124963 person years for all controls. Comorbidities (congestive heart failure, chronic obstructive pulmonary disease, coronary artery disease, stroke, chronic renal failure, chronic liver disease, and pre-diagnosis arterial and venous thromboses were significantly higher in cases as compared to controls (p The mean per-patient-year direct medical cost of treatment for patients with ET was $18,840 (2.3 X controls), for PV $18,966 (2.2 X controls) and for MF, $38,147 (4.5 X controls). Factors impacting costs of treatment are summarized in Table 1. In all MPNs, increased health expenditure was associated with older age (>65 years), those who never consulted a specialist in hematology-oncology, and increasing morbidity denoted by ADG score. Patients who were first seen by the specialist >6 months after the diagnosis incurred significantly lesser cost of treatment due to less comorbidity burden as noted by the lower ADG score for patients with >6 months vs CONCLUSION: MPN patients have substantial higher direct medical cost of treatment compared to matched-controls and have a high co-morbidity burden at diagnosis that significantly predicted higher cost of treatment. After adjusting for co-morbidity, history of venous thrombosis at diagnosis showed significantly higher cost of treatment in ET and PV. In addition, MPN patients who were never referred to a specialist incurred significantly higher cost of treatment. Disclosures Gupta: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding; Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Background: Although frailty influences outcomes in hematologic oncology, little is known about the feasibility and impact of embedded geriatric consultation for frail older adults with blood cancers. Methods: From February of 2015 until May 2018, all patients aged 75 and older presenting for initial consultation for hematologic malignancy at the Dana-Farber Cancer Institute (DFCI) were approached for geriatric screening by a trained clinic assistant. In a 15-minute interview, the assistant used two parallel methods-the phenotype approach (Fried, J Geront A Biol Sci Med Sci, 2001) and the cumulative deficit approach (Rockwood, J Geront A Biol Sci Med Sci, 2007) -to characterize patients as "frail," "pre-frail," or "robust." Patients determined to be frail of prefrail on at least one of the two screening methods who had a scheduled oncology follow-up at DFCI were then randomized to have tandem consultation with an embedded board-certified geriatrician; the schema used an unbalanced allocation design powered to detect differences in one-year overall survival. Patients were followed for hospitalizations and emergency department visits in the first six months after enrollment, documented discussions about goals of care at the end of life during the first year by any DFCI outpatient provider (resuscitation status, hospice, or preferred location for dying using criteria from Mack, Ann Intern Med, 2012), and one-year overall survival. We also undertook a survey of the 65 oncologists and physician extenders who had utilized geriatric services, asking them about consultation usefulness (on a Likert scale where 1= "least" and 5 = "most" useful) for evaluating cognition, informing treatment decisions, connecting patients to resources, and managing non-oncologic comorbidities. We conducted pairwise analyses using McNemar's test to identify the most useful services. Results: Of 186 patients approached, 160 enrolled, with 60 randomized to geriatric consultation and 100 to usual care. Mean age was 80.4 years, 65% were male, and 30% were initially seen in the MDS/leukemia clinic, 31% in the lymphoma clinic and 39% in the myeloma clinic. Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with an embedded geriatrician (95% CI [68%, 88%]). Among the 12 who did not, 3 died before the scheduled consultation, 6 ultimately did not to return to DFCI, and 3 cancelled their geriatric appointments. In an intent-to-treat analysis, patients assigned to consultation were no less likely to die within one year (Figure; HR 0.99, 95% CI [0.58, 1.68]). Results were also not significant in as-treated analysis (HR 0.87, 95% CI [0.49, 1.55]). In negative binomial regression analysis, patients assigned to geriatric consultation had modestly fewer unplanned hospitalizations and emergency room visits than those randomized to usual care, but the results were not significant. The odds of having a documented discussion about goals of care for patients randomized to geriatric co-management were 2.66 (95% CI [0.95, 7.41]; p=.06) times versus for those receiving usual care; for those who actually completed a geriatrician visit, they were 3.07 (95% CI [1.06, 8.82]; p=.04). Of 65 providers surveyed, 37 responded (57%). Mean responses in the "5 = most useful" category for each question were as follows: managing non-oncologic comorbidities 60%, connecting patients to resources 57%, evaluating cognition 49%, and informing treatment decisions 34%. McNemar's tests revealed that managing non-oncologic comorbidities was no more likely to be considered "most useful" than connecting patients to resources (p=.48) and evaluating cognition (p=.06) but more likely than informing treatment decisions (p=.01). Connecting patients to resources was no more likely to be considered "most useful" than evaluating cognition (p=.37) but more likely than informing treatment decisions (p=.04). Conclusion: Embedded geriatric consultation for frail and pre-frail older adults with blood cancers is feasible but may not affect acute care utilization or survival in the first year. In contrast, consultation likely has a substantial impact on the timeliness of discussions about goals of care at the end of life. Oncology providers report that embedded geriatric consultation is useful among many care domains, but most helpful for managing comorbidities and connecting patients to resources. Figure Disclosures Stone: AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy; Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; Novartis, Agios, Arog: Research Funding. Soiffer:Kiadis: Other: supervisory board; Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Jazz: Consultancy; Cugene: Consultancy; Mana therapeutic: Consultancy.

To be useful to policymakers and stakeholders, cost-effectiveness analyses (ceas) should be published in a timely manner and without bias. The aims of the present study were to examine the time between conference abstract presentation and subsequent publication, to determine the factors associated with time to publication, to evaluate potential publication bias, and to examine discrepancies in the results between abstract and publication. Abstracts of ceas presented at the annual meetings of the American Society of Clinical Oncology (asco), the American Society of Hematology (ash), and the International Society for Pharmacoeconomics and Outcomes Research (ispor) between 1997 and 2007 were reviewed. Time-to-event analysis was performed to assess the timeliness of publication and to examine factors associated with time to publication. Summary statistics were used to assess discrepancies in incremental cost-effectiveness ratios (icers) between abstract and publication. Of 164 abstracts identified, 65 (39.6%) were subsequently published. The 1-, 2-, 3-, and 5-year publication rates were 12.8%, 25%, 34.2%, and 40.5% respectively. Abstracts were more likely to be published if presented at asco than at ispor (hazard ratio: 1.94, p = 0.038). There was no direct evidence of publication bias for abstracts with favourable icers. Comparing icers between abstracts and publications, the mean absolute difference was 23.8%, 50% of studies had a change in icer exceeding 10%. Publication rates for ceas were low, and publication was not timely with respect to informing the decision-making process for funding. Abstract results often differed from publication results and cannot reliably be used in the decision-making process for funding.

Background: Azacitidine (AZA) use in higher-risk MDS has been adopted because it improves survival. Despite this, "real-world" data on the economic impact and resource utilization remains unknown. We used the Ontario provincial AZA MDS registry, which captures all AZA-treated patients in the province, to analyze "real-world" data on healthcare use, associated costs and their predictors in AZA treated higher-risk patients. Methods: We linked the provincial MDS AZA registry (single-payer/universal access), which captures baseline characteristics and treatment response for all AZA-treated patients in Ontario, to population-based health system administrative databases. Only higher-risk MDS patients (IPSS intermediate-2, high) and low blast count AML (21-30% blasts) treated from May 30, 2010 to March 16, 2015 were included. Patients were followed for 24 months following first AZA treatment and censored at the earliest of 90 days after last AZA treatment, date of death, time of acute leukemia induction/allogeneic stem cell transplant or March 31, 2016. We estimated healthcare resource utilization and the mean (and overall) standardized 28-day healthcare cost in Canadian dollars ($1 CDN = 0.76 USD$). Quantile regression was used to explore predictors of cost. Negative binomial regression models were used to explore predictors for higher rate of emergency department (ED) visits, and for longer length of stay, with the natural logarithm of length of follow-up as an offset variable in each model. Results: The registry had 652 higher-risk MDS and 225 low blast count AML patients (n = 877) with median follow up of 8 months (IQR 4-13). Median age was 73 years (IQR 66-79), 66.0% were male, 17.8% were secondary MDS and IPSS scores of those calculable were intermediate-2 (64.9%) and high-risk (35.1%). At the time of AZA initiation, 587 patients (66.9%) were transfusion dependent. The median number of cycles received was 6 (range 3 to 11) and median overall survival was 16.1 months (95% CI 13.9 to 18.3). Overall, 705 patients (80.4%) had at least 1 ED visit and 290 (33.1%) had an ED visit during their first cycle of AZA. In addition, 680 patients (77.5%) had at least 1 hospital admission with a mean hospital stay of 17.7 days (95% CI 16.3 to 19.1) over the entire study period. 141 patients (16.1%) required admission to an intensive care unit. Older age (Rate ratio [RR] = 1.33, 95% CI 1.09-1.62), rurality (RR=1.75, 95% CI 1.42-2.15), high IPSS score (RR=1.31, 95% CI 1.06-1.62), and increased comorbidity level were each independent predictors of increased ED visits; while higher comorbidity level (RR=1.51, 95% CI 1.08-2.11), high IPSS score (RR=1.39, 95% CI 1.01-1.92), and transfusion dependence (RR=1.51, 95% CI 1.13-2.01) were associated with longer hospital stays. The overall mean cost was $146,675 per patient (95% CI $139,537 to $153,812) including AZA and $103,580 (95% CI 98,675 to 108,486) excluding AZA drug costs. The mean standardized cost per 28-day period per patient was $17,638 (95% CI $16, 870 to $18,407) with AZA and $13,450 (95% CI $12,730 to $14,170) without AZA drug costs. Inpatient admissions ($4,631, 95% CI $4,010 to $5,251) and non-physician outpatient cancer clinic costs ($6,092, 95% CI $5,851 to $6,333) were the major cost drivers. Excluding AZA costs, the mean standardized 28-day costs were higher in those receiving less than 4 cycles of AZA (n= 295) at $19,408 (95% CI $17,568 to $21,248), compared with those receiving 4 or more cycles (n= 582) at $10,430 (95% CI $10,069 to $10,790) with inpatient admissions as the major driver (mean $10,192, 95% CI $8,594 to $ 10,192 vs. $1,812, 95% CI $1,558 to $2,065). On multivariable analysis, only greater comorbid disease burden (β = $2,074, 95% CI $665 to $3,483) and transfusion dependence (β = $2,402, 95% CI $1,190 to $3,613) were associated with higher median standardized 28-day cost. Conclusions: In our analysis of "real-world" patients with uniformly higher-risk MDS treated with AZA we demonstrate a significant economic impact above and beyond the cost of AZA alone. The costs are higher in patients who are transfusion dependent and have greater comorbidity and appear to be driven by inpatient care and outpatient non-physician ambulatory care. This group of patients are high users of healthcare resources with the majority having ED visits and inpatient admissions. These results will inform patients and providers about the "real-world" anticipated toxicities of AZA. Disclosures Buckstein: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Dabigatran is a direct thrombin inhibitor recently approved in the United States and Canada for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Although dabigatran is administered as a fixed dose, does not interact with foods, and has fewer drug interactions than warfarin, the risk of hemorrhagic complications is similar for these two drugs. 1,2 There is no specific reversal agent for dabigatran, and reversal of coagulopathy in the event of severe hemorrhage can be challenging. With growing use of dabigatran for long-term anticoagulation, it is important that acute care providers have a standardized and evidence-based approach to treating patients with severe hemorrhage secondary to dabigatran. We report a case of severe gastrointestinal hemorrhage related to dabigatran and discuss the management of severe hemorrhage in this context.

Follicular lymphoma (FL) is characterized by an initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progression during rituximab-based chemoimmunotherapy, rituximab maintenance or within 6 months of treatment completion. Our primary outcome was time to early progression (CIR resistance). Between July 2006 and April 2010, 132 patients met the inclusion criteria and 22 (16.7%) demonstrated CIR resistance with a median follow-up of 33 months. High-risk Follicular Lymphoma International Prognostic Index (FLIPI) score was predictive of CIR resistance (hazard ratio [HR] 2.43; 95% confidence interval [CI], 1.4-4.1; p = 0.001). Overall, eight patients (36.3%) transformed (biopsy-proven), with no transformation in the chemoimmunotherapy responder group. Median overall survival in the CIR resistant group was 47 months. Patients with CIR resistance had high rates of histologic transformation and shorter survival with poor response to next therapy.

Background: In the AZA-001 trial, azacitidine (AZA) altered the natural history of patients with higher-risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival compared to conventional care regimens (24.5 months versus 15.0 months). Once approved for drug reimbursement by the provincial health ministry, Cancer Care Ontario (CCO) mandated that all eligible patients be enrolled in a prospective registry to ensure compliance with eligibility criteria and schedules of drug administration. Baseline characteristics were recorded and treatment response were to be submitted every 6 cycles of treatment. Our objectives were to audit this clinical program for results after 6 years and identify the prognostic markers for survival in a homogenous higher-risk MDS/low blast count AML patient population. Methods: Only higher-risk MDS patients (intermediate-2, high) as defined by the International Prognostic Scoring System (IPSS) and low blast count AML (20-30% blasts) treated with AZA in Ontario, Canada from June 1, 2010 to March 2, 2016 were eligible and included. Our primary outcome was overall survival (OS) from date of first AZA treatment. Our secondary outcomes were overall response rates and the predictors of OS including administration schedules, centre size or type (regional cancer versus community). Univariate and multivariable Cox proportional hazard model were used to determine the predictors of OS. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: 825 higher-risk MDS and 276 low blast count AML were included (n = 1101 total). Median age was 74 years (range 19 to 99), 65.2% were male and the IPSS scores were intermediate-2 (64.3%) and high-risk (35.7%). Sixty-six percent of patients were transfusion dependent (TD) at time of AZA initiation and 15.5% had received previous chemotherapy. By dosing schedule, 24.7% received AZA for 7 consecutive days (7d), 12.4% for 6 consecutive days (6d) and 62.9% by the 5-2-2 schedule. Overall, the median number of cycles received was 6 (range 1 to 67) and 8 (range 6 to 14) when restricted to the 692 (63%) patients who received at least 4 cycles of treatment. Dose reductions were seen in 33.3% of patients (mean 11.1 mg/m2 in those with reductions) and were more common over time (negative slope 0.178; p < .0001). Of those with repeat bone marrow (n = 293) best response was complete response (CR) in 16.7% and partial response (PR) in 10.6%. Of those without CR/PR/progressive disease on bone marrow (n = 814), 20.4% experienced hematologic improvement including those with marrow CR and marrow stable disease. The actuarial median survival was 11.6 months (95% CI 10.7- 12.4) with a significantly longer OS for MDS compared with low blast count AML (12.4 months vs. 9.6 months; p = .0002) and 16.7 months (95% CI 15.2-18.1) for those receiving at least 4 cycles. There was no difference in OS between the 3 dosing schedules (11.7 months (7d) vs. 10.2 months (6d) vs. 12.0 months (5-2-2); p = .87; figure 1A), regional cancer centre vs. community (11.3 months vs. 11.7 months; p = .19; figure 1B) or by centre volume (11.4 months < 50 patients vs. 11.6 months > 50 patients; p = .38; figure 1C). On univariate analysis, the following were predictive of OS: blast percentage, number of cytopenias, karyotype, IPSS, WHO classification, TD, greater transfusion burden and secondary MDS. The multivariate model with the highest R2 (13.5%) included blast percentage (p < .0001), karyotype (p < .0001), cytopenias (p = .038), TD (p < .0001) and secondary MDS (p = .0006) as summarized in the table below. Conclusions: In our large real world evaluation of AZA use in higher-risk MDS/low blast count AML, we validated the expected overall response rates to AZA but demonstrated a lower than expected OS compared to the AZA-001 trial. Reassuringly, survival did not differ by dosing schedules, centre volumes or center type (regional cancer vs. community). OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realized. This represents the largest real world evaluation of AZA in higher-risk MDS/low blast count AML and additional analyses are underway. Table Table. Figure 1 Figure 1. Disclosures Mozessohn: Celgene: Honoraria. Buckstein:Celgene: Honoraria, Research Funding; Novartis: Honoraria.

Background Metabolic syndrome (MetS) is a risk factor for development of cancer. Because aberrant lipid metabolism is a pathogenic feature of chronic lymphocytic leukemia (CLL), our objective was to determine if CLL patients have a higher prevalence of MetS preceding diagnosis and to determine the impact of lipid-lowering medications on survival. Methods We conducted a population-based case-control study in Ontario, Canada, using administrative databases of adults age 66 years and older to compare the prevalence of MetS preceding CLL with age- and sex-matched control subjects. Logistic regression was used to study the association between MetS and its components to CLL. The Kaplan-Meier method and Cox Regression were used to investigate survival. All statistical tests were two-sided. Results We identified 2124 persons with CLL and 7935 control subjects from January 1, 2000, to December 31, 2005, with follow-up until March 31, 2014, three years from the date of last contact with the health care system, or death. The mean age was 75.6 years, 20.2% had diabetes, 35.8% had hypertension, and 17.6% had dyslipidemia. In multivariable analysis, dyslipidemia (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.44, P < .001) and hypertension (OR = 1.12, 95% CI = 1.01 to 1.25, P = .03) were associated with the development of CLL, whereas MetS and diabetes were not. Lipid-lowering medication was associated with a statistically significant improved survival in patients with CLL (HR = 0.53, 95% CI = 0.47 to 0.61, P < .001). Conclusions We demonstrate a higher prevalence of dyslipidemia preceding a diagnosis of CLL compared with control subjects, supporting preclinical data. Lipid-lowering medications appear to confer a survival advantage in CLL. Prospective studies are needed to confirm these results and test their potential as therapeutic applications.

Background: Metabolic syndrome (MetS) is a risk factor for the development of cancer. Pre-clinical data suggests that chronic lymphocytic leukemia (CLL) cells are dependent on adipocytes and fatty acids for growth and that aberrant lipid metabolism is an important pathogenic mechanism in CLL. Our objective was to determine whether patients with CLL have a higher incidence of MetS prior to their CLL diagnosis compared to those without CLL and to determine the impact of lipid-lowering medications including statins on survival. Methods: We conducted a population-based retrospective cohort study in Ontario, Canada using administrative databases (i.e., Ontario Cancer Registry, Ontario Drug Benefit dataset, Aggregated Diagnostic Groups (ADGs), postal codes/income) of adults >66 years old to compare the prevalence of MetS and its components (diabetes, dyslipidemia, hypertension) in CLL patients that preceded their diagnosis. This was compared to age and sex-matched controls without CLL. Logistic regression was used to study the association between MetS and its components to CLL, adjusting for location (rural vs. urban), disease comorbidity burden (ADGs) and socioeconomic status. The Kaplan-Meier method was used to illustrate survival. Results: We identified 2,124 persons with CLL and 7,935 controls from January 1, 2000 to December 31, 2005 with follow-up until death or March 31, 2014. The mean age was 75.6 and 42.1% were female. Overall, 14.1% had diabetes, 63.1% had hypertension and 28.0% had dyslipidemia. On univariable analysis, only dyslipidemia alone (OR 1.35; 95% CI 1.21 to 1.50) and the combination of diabetes and dyslipidemia (OR 1.18; 95% CI 1.00 to 1.39) were associated with the development of CLL, whereas MetS and diabetes alone were not. On multivariable analysis only dyslipidemia was independently significant (OR 1.30; 95% CI 1.16 to 1.47; see table). Notably, on univariable survival analysis the use of lipid-lowering agents comprised primarily of statins at any time (prior or subsequent to CLL diagnosis) was associated with a significantly improved median overall survival in patients with CLL (7.9 years, 95% CI 7.3 to 8.5 vs. 4.1 years, 95% CI 3.7 to 4.5 years; p < 0.0001; see figure 1). Conclusions: We demonstrate a higher prevalence of dyslipidemia preceding a diagnosis of CLL compared to controls, supporting pre-clinical data. Also, the association of MetS and CLL appears to be driven primarily by dyslipidemia. Lipid-lowering medications and in particular statins appear to confer a survival advantage in CLL. Further multivariable survival analysis and ultimately prospective studies are needed to confirm these results and test their potential application to intervention strategies. Table. Exposure Odds Ratio (CLL vs. Control) metabolic syndrome 1.10 (95% CI 0.92 to 1.32) diabetes + dyslipidemia 1.17 (95% CI 0.98 to 1.40) diabetes 1.03 (95% CI 0.90 to 1.17) dyslipidemia 1.30 (95% CI 1.16 to 1.47) Figure 1. Figure 1. Disclosures Spaner: Roche: Honoraria; Lundbeck: Honoraria; Novartis: Research Funding; Janssen: Honoraria. Buckstein:Celgene: Honoraria, Other: Advisory Board.

Background: The role of combined modality therapy (CMT) in previously untreated patients with primary central nervous system lymphoma (PCNSL) remains unclear. We performed a systematic review of the available evidence regarding the efficacy and long-term neurotoxicity of consolidative radiation therapy in addition to systemic chemotherapy in the upfront management of fit immunocompetent adult patients with PCNSL. Methods: Peer reviewed literature searches were conducted using the MEDLINE, EMBASE and PubMed databases from 1950 to March 26, 2015. We included all prospective clinical trials (randomized and non-randomized) published on or after January 1, 1998 with at least 20 subjects receiving frontline CMT with CNS-penetrating chemotherapy in addition to radiation therapy. We excluded trials of high-dose chemotherapy followed by autologous stem cell rescue and those involving patients with isolated intra-ocular lymphoma. The primary outcome was overall survival (OS). Secondary outcomes included progression free survival (PFS), overall response rate (ORR), complete remission (CR) rate, partial remission (PR) rate, and incidence of late radiation-induced neurotoxicity. Two reviewers independently performed title and abstract screening, full-text review and data extraction. The Cochrane Risk of Bias Tool was used to assess the quality of randomized trials included in this systematic review. Results: The literature search yielded 10,646 potentially relevant records for primary screening after de-duplication, of which 299 full-text articles were evaluated. Of the 299 full-text articles reviewed, there were 21 publications eligible for inclusion. These 21 publications represented 15 unique clinical trials (4 trials were reported in 2 publications each, and 1 trial was reported in 3 publications; Figure 1). The included studies involved a total of 1123 enrolled subjects. Of the 15 trials included, there was 1 phase III randomized controlled trial, 1 phase II randomized trial, and 2 non-randomized multi-arm trials. The remaining studies were single arm non-comparator trials. Chemotherapy backbones varied, and planned whole brain radiation therapy (WBRT) doses ranged from 23.4 to 50.4 Gy. Due to variation in follow-up time, it was difficult to compare survival endpoints between studies. In the large multicenter phase III randomized controlled trial comparing 202 patients receiving WBRT to 208 patients without WBRT, there was no difference in OS (32.4 months vs. 36.1 months, p=0.98) however WBRT improved PFS from 9.9 months to 15.4 months (p=0.034) (Korfel et al., Neurology. 2015 Mar 24;84(12):1242-8). Response rates were not consistently reported after completion of both chemotherapy and radiation therapy. Amongst those trials reporting response rates after completion of CMT, the CR rate ranged from 28-87% and the ORR ranged from 56-100%. Although there was variability in the definitions and reporting of delayed-onset neurotoxicity, this complication was common, ranging from 0-45.8%. The Cochrane Risk of Bias Tool was only applicable to the 2 randomized trials in this review. On the basis of clinical heterogeneity, we chose not to statistically pool the results of the included trials together in this systematic review. Conclusions: We identified a large body of literature assessing the use of CMT in the upfront management of PCNSL. However, only one randomized study addressed the specific role of consolidative radiation therapy with respect to survival, in which there was no benefit to OS. Consolidative WBRT may improve local disease control and PFS, though late neurotoxicity remains a concern. Our review underscores the need for ongoing collaborative efforts between treatment centers to design and conduct large randomized controlled trials. Figure 1. PRISMA Flow Diagram Figure 1. PRISMA Flow Diagram Disclosures Buckstein: Celgene: Honoraria, Research Funding.

Background:The American Society of Hematology Practice Improvement Modules (ASH PIMs) are online tools designed for clinicians to monitor the quality of care in their practice. The ASH PIM for non-Hodgkin lymphoma (NHL) was designed by a committee of NHL experts and was recently released in the ASH Academy. The ASH PIM for NHL defines quality metrics in six areas: pathological diagnosis, staging, Hepatitis B testing, use of growth factors, vaccination, and fertility counseling. Objectives:1) Use the ASH PIM for NHL to measure quality of care at 4 cancer centers in the Greater Toronto Area. 2) Assess the feasibility, reliability, and usefulness of the ASH PIM for NHL. Methods:To measure quality of care, 78 patients undergoing first line chemotherapy for NHL were reviewed at 4 cancer centers (3 academic centers and 1 community center) near Toronto, Canada. Two hematology fellows independently scored each patient chart for the 6 quality metrics in the ASH PIM. After data collection, interviews (using structured questionnaires) were conducted with the chart reviewers as well as with physicians experienced at treating NHL. Results: Three out of the 4 cancer centers had high performances (>90%) in pathological diagnosis and staging. Two of the 4 centers had high performances for Hepatitis B testing. Zero of the 4 centers had high performances for documenting growth factor use, vaccinations and fertility counseling. A feasibility questionnaire revealed that each chart required 15 minutes for review. Reviewers noted that the ASH PIM for NHL was clear for how to score pathological diagnosis, staging, and hepatitis B testing (mean score >4 out of 5 for clarity), but unclear for how to score the use of vaccinations (mean 2.3/5). Reviewers were able to accurately score pathological diagnosis, staging, and hepatitis B (mean >4/5 for perceived accuracy), but were unable to accurately score vaccination and fertility counseling (mean Of the 6 metrics, experienced NHL physicians rated pathological diagnosis and staging as most important, with vaccination and growth factor use rated as least important. When provided with the performance data for their own center, the results were perceived to accurately reflect patient care in 5 out of 6 of the metrics. Performance on fertility counseling was thought to be under-estimated due to poor documentation. Overall, the ASH PIM for NHL was perceived to capture the quality of patient care moderately well. Areas not captured by the ASH PIM, but perceived to be important to NHL patient care included: the reduction of delays between lymphoma suspicion and first treatment, patient satisfaction, and advanced care planning. Conclusions: The ASH PIM for NHL is feasible, reliable, and measures a number of important aspects of patient care. Some metrics could be made clearer by including more explicit definitions. Performance on the metrics relying on clinical documentation was not as high as for those relying on objective testing. The performance of cancer centers in the Greater Toronto Area on the ASH PIM for NHL suggests specific areas for quality improvement at each center. Disclosures Hicks: Gilead: Research Funding.

Objectives: The objectives of this study were to examine healthcare providers' knowledge of the transmissibility of sexually transmitted infections (STIs) and identify knowledge determinants. Study: Questionnaires were completed March through May 2004 by a representative sample of Canadian healthcare providers, yielding a corrected response rate of 50.8% for physicians. STI workers returned 236 questionnaires. Results: For physicians, the distribution of HIV estimates was positively skewed (mode = 10%), whereas chlamydia estimates were widely dispersed. STI workers showed a trimodal (0%, 50%, and 100%) distribution of HIV estimates and a negatively skewed distribution of chlamydia estimates (mode = 100%). Overall, 1.4% (HIV) and 5.8% (chlamydia) of respondents gave estimates close to the actual transmission probabilities. More years of medical experience and higher estimates of STI prevalence predicted higher transmissibility estimates (95% confidence intervals). Conclusions: That only a small percentage of healthcare providers are aware of the actual transmissibility of HIV and chlamydia has implications for improving medical and sexual health training.

228 Background: Patients with hepatitis B virus (HBV) who are HBsAg+ are at risk of HBV reactivation if rituximab is administered in the absence of antiviral treatment. Recently, it has been reported that patients with so-called “resolved HBV infection”(HBsAg-/cAb+) may also be at risk; however, the degree of risk is not known. Methods: We performed a systematic review of the English and Chinese language literature in Medline (1996 to June week 3 2013) and Embase (1996 to 2013 week 26) using the MeSH terms “lymphoma” and “hepatitis B”. Eligible studies were limited to those reporting primary data on HBV reactivation rates in HBsAg-/cAb+ patients receiving rituximab. We excluded case series with less than 5 patients. Pooled estimates were calculated for HBV reactivation and the impact of HBsAb status on HBV reactivation rate was explored. We also examined reactivation in HBsAg+ patients receiving rituximab by performing a systematic review of the English language literature in PubMed (1997 to June 21, 2013) using the terms “hepatitis B virus”, “reactivation” and “lymphoma”. Results: Data from 550 HBsAg-/cAb+ patients in 12 studies were included. Using a standardized definition of HBV reactivation, (increase in HBV DNA from baseline or HBsAg seroreversion +/- ALT >3 x upper limit of normal), the pooled estimate for the risk of HBV reactivation in HBsAg-/cAb+ patients was 8.1% (I2 = 55%, P = 0.007). Significant heterogeneity was apparent. Exploratory analyses suggested that patients were less likely to reactivate if they were HBsAb+ (OR = 0.32; 95% CI 0.12-0.85, P = 0.0285). In HBsAg+ patients we meta-analyzed prospective, controlled studies. Without antiviral prophylaxis, the reactivation rate for HBsAg+ lymphoma patients was 51.0% (I2 = 0%, P = 0.93). Conclusions: Our meta-analyses confirm that there is a risk of HBV reactivation in HBsAg-/cAb+ patients exposed to rituximab. HBsAb+ patients may be at lower risk than those who are HBsAb-. However, heterogeneity in the risk estimates limits their generalizability. Without prophylaxis, significant reactivation in HBsAg+ patients exists. Large prospective studies are needed to clarify the risk of HBV reactivation in HBsAg-/cAb+ patients and to inform decisions about best practice.

6592 Background: Patients with hepatitis B virus (HBV) who are HBsAg+ are recognized to be at risk of HBV reactivation if rituximab is administered in the absence of antiviral treatment. Recently, it has been reported that patients with so-called “resolved HBV infection”(HBsAg-/cAb+) may also be at risk; however, the degree of risk is not known. Methods: We performed a systematic review of the English and Chinese language literature in Medline (1996 to July week 2 2012) and Embase (1996 to 2012 week 29) using the MeSH terms “lymphoma” and “hepatitis B”. Eligible studies were limited to those reporting primary data on HBV reactivation rates in HBsAg-/cAb+ patients receiving rituximab. We excluded case series with less than 5 patients. Pooled estimates were calculated for HBV reactivation and the impact of HBsAb status on HBV reactivation rate was explored. Results: Data from 445 patients in 12 studies were included. Using a standardized definition of HBV reactivation, (ALT >3 x upper limit of normal AND either an increase in HBV DNA from baseline OR HBsAg seroreversion), the pooled estimate for the risk of HBV reactivation in HBsAg-/cAb+ patients was 5.4% (I2 = 63%, P = 0.009). Significant heterogeneity was apparent. Exploratory analyses suggested that patients were less likely to reactivate if they were HBsAb+ (OR = 0.32; 95% CI 0.12-0.85, P = 0.0285). Conclusions: Our meta-analysis confirms that there is a measurable risk of HBV reactivation in HBsAg-/cAb+ patients exposed to rituximab HBsAb+ patients may be at lower risk than those who are HBsAb-. However, heterogeneity in the risk estimates limits their generalizability. Large prospective studies are needed to clarify the risk of HBV reactivation in HBsAg-/cAb+ patients and to inform decisions about best practice.

A 60-year-old woman presented with subacute progressive lower extremity weakness. This was associated with a 40lb weight loss and fevers. She was previously healthy, aside from renal transplantation 9 years earlier for end stage renal disease resulting from IgA nephropathy. On examination, she had clubbing, a single lymph node in the right cervical chain, and objective findings of lower extremity weakness with lower motor neuron findings. Investigations revealed a thrombocytosis and elevated CSF protein. Electromyographic evidence of diffuse polyradiculopathy with demyelination was documented. On imaging, she had a large lytic/sclerotic lesion in the right scapula measuring 8 cm, a pericardial effusion, and borderline splenomegaly. Pathological assessment of the excised lymph node revealed Castleman-like changes; biopsy of the right scapular lesion revealed λ-restricted plasma cells, in the absence of a monoclonal protein in the bone marrow or periphery. A diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) with plasmacytoma was established; a post-transplant lymphoproliferative disorder was suspected.

Abstract 4981 Follicular lymphoma (FL) is an indolent lymphoma characterized by slow growth, initial response to treatment with inevitable relapse. Recent trials have demonstrated improved progression free survival (PFS) with rituximab-containing induction, maintenance rituximab (MR) or both. However, a small subset of patients (pts) will show disease progression during the induction or maintenance phase. We evaluated rituximab resistance (RR) including incidence, predictors, rate of transformation and prognosis for pts demonstrating RR. We defined RR as disease progression during induction, maintenance or within 6 months of last dose of rituximab. We retrospectively identified pts who received rituximab for symptomatic FL from July 2006 to April 2010 at 2 regional cancer centres. Those with a diagnosis of FL grades 1, 2 or 3a with first exposure to rituximab (induction, maintenance or both) were included. Exclusion criteria included FL grade 3b and previous rituximab exposure. Progression was ascertained from clinical notes or radiological investigation as per IWG Criteria (1999). Transformation was defined by confirmatory biopsy and clinical suspicion of transformation was also recorded (nodal growth, rapid rise in LDH or new B symptoms). PFS and overall survival (OS) were measured from initiation of rituximab induction. Log-rank statistics were used to identify univariate predictors for RR and Cox regression for multivariate analysis with outcome as time to early progression (RR). Of the pts screened, 132 met inclusion criteria (112 pts receiving primary therapy, 20 for ≥ 2nd line therapy); 22 pts (16.7%) demonstrated RR. Incidence of RR was similar for pts receiving primary therapy (17.0%). Pt characteristics for rituximab sensitive (RS) and RR groups are shown in Table 1. From induction, median follow-up was 33 months (range 9 to 61 months). In univariate analysis, high risk FLIPI score at induction was predictive of RR (p = 0.002). Partial response to induction (p = 0.082) trended to significance. Other factors not predictive of RR included: age, gender, high grade histology (grade 3a), previous chemotherapy received, time from diagnosis to induction therapy and anthracycline-based induction. A Cox regression model was constructed with FLIPI score and anthracycline-based induction as covariates. FLIPI score was independently and significantly predictive of RR (HR 2.43; 95% CI, 1.4 to 4.1; p = 0.001). Of the 22 pts who were RR, 18 (81.8%) required subsequent chemotherapy with only 9 achieving at least a partial response. Ten pts (45.5%) required more than 1 line of chemotherapy post-progression with a median time to next line of therapy of 9 months (95% CI, 2.9 to 15.1; see figure). Among the RR pts, 5 (22.7%) showed evidence of transformation on biopsy at initial resistance and an additional 3 (13.6%) were clinically suspected. Within 12 months of resistance, a further 3 pts in the RR group demonstrated biopsy-proven transformation. Overall, 10 pts (45.5%) transformed (biopsy-proven) with no transformation in the RS group. During follow-up, 9 deaths occurred, all in those with RR, 5 following biopsy-proven transformation. The median PFS and OS in the RR group were 17 months and 47 months, respectively. Table 1 Characteristics RS (n = 110) RR (n = 22) Age (MEAN) 58.9 58.9 Gender (females) 43.6% 40.9% High histological grade (3a) 8.4% 9.1% Previous treatment (yes) 15.5% 13.6% Alkylator 11.8% 13.6% Number of lines of previous treatment >1 4.5% 4.5% Mean time from diagnosis to induction (months) 30.3 28.1 Induction chemo R-CVP based 78.2% 86.4% R-CHOP based 18.2% 9.1% Other 3.6% 4.5% Response to induction PR 77.3% 72.7% CRu 12.7% 0% CR 10.0% 4.5% SD/PD 0% 22.7% FLIPI score at induction Low (0, 1, 2) 57.8% 18.2% Intermediate (3) 26.6% 40.9% High (4 or 5) 15.6% 40.9% Stage 3 or 4 88.2% 100% High tumor burden at diagnosis (GELF criteria) 43.6% 40.9% We demonstrated that the incidence of rituximab resistance in FL on first exposure to rituximab in our population was 16.7%. FLIPI score was predictive for RR and was independent of anthracycline-based induction regimens. Pts with RR had a high rate of histologic transformation (36.3% within 12 months post RR) and a shorter PFS/OS with a poor response to next therapy. Biopsies to confirm transformation should be performed in all pts demonstrating RR, and new therapies are needed for this group of pts. Disclosures: Crump: Ortho Johnson & Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kukreti:Celgene: Honoraria; Ortho Biotech: Honoraria; Roche: Honoraria.