ALBERT

Description: Background: Health-Related Quality of life (HRQoL) is diminished in patients with myelodysplastic syndrome (MDS). We have previously shown that HRQoL remains stable over time and low hemoglobin, transfusion dependence (TD) and age 〉 65 years impact QoL1. Here, we present an updated larger data set with longer follow up and consider the impact of baseline characteristics and treatments received on patient-related outcomes. Methods: MDS-CAN is a prospective database active in 15 centers across Canada, enrolling patients since April 2012. In addition to disease and patient-related characteristics, we measure HRQoL at baseline and every 6 months using the EORTC-QLQ-C30, EQ-5D, and a global fatigue scale (GFS). We examined the impact of disease related factors (IPSS, IPSS-R, karyotype, TD), patient factors (ECOG, age, gender, co-morbidity (Charlson index), frailty (Rockwood scale), disability (Lawton-Brody Independent Activities of Daily Living), and treatments received at any time (azacitidine (AZA), lenalidomide, erythropoietin-stimulating agents (ESA), iron chelation) on QoL scores. AZA-treated patients were divided into responders (where documented) or deriving benefit (if 〉 6 cycles) vs. non-responders. Wilcoxon rank-sum or Kruskal-Wallis nonparametric tests were used to compare scores among subgroups. Changes in QoL were assessed with a linear mixed model to account for time- dependent covariates such as TD, risk scores and treatment. Results: 594 patients were enrolled a median of 2.2 months post diagnosis (IQR: 0.8, 4.8) with a median age of 73 years , 63% male gender and performance status (ECOG) of 0-1 in 90%. IPSS scores were low/int-1 in 73% and IPSS-R scores were very low (9%), low (30%), intermediate (27%), high (20%) and very high (14% of patients). 31% were transfusion dependent at enrolment. Treatments received at any time included AZA (38%), lenalidomide (9.8%), ESA (35%) and iron chelation (12%). At a median follow up of 17 months, 329 patients (55%) died with cause of death reported as AML in 22%. Baseline assessment: Mean EQ-5D global score for the cohort was 0.75 ± 0.25 and did not significantly change over time (Figure 1). Patients with high IPSS, high/very high IPSS-R, TD, lower hemoglobin, higher ECOG, increased comorbidity, frailty and disability were more likely to have lower EQ-5D/QLQ C30 scores (inferior QoL) and higher fatigue (GFS). Age was not significantly related to QoL. Interestingly, female gender was associated with inferior QoL by EQ-5D and GFS (Figure 2). Patients scoring in the lowest quartiles for physical performance tests (grip, 4 metre walk and 10x chair sit-stand tests) also had inferior QoL scores. QoL over time: By linear mixed modelling, we did not find significant differences in QoL over time in patients treated with or without AZA, lenalidomide, or ESAs measured by the EQ-5D instrument. Iron chelation was associated with lower scores (p=0.003) although this may simply be a surrogate for transfusion dependence which is associated with inferior QoL. AZA responding/deriving benefit patients had higher QoL scores from baseline and decreased fatigue compared with those not responding or not deriving benefit (Figure 3) measured by the QLQ-C30 and GFS instruments. Patients with the highest IPSS/IPSS-R risk groups had significantly inferior QoL over time. In conclusion, this study demonstrates that HRQoL remains fairly stable over time in MDS and implementation of treatment is not at the detriment of patient related outcomes. Patients treated with AZA who respond or remain on drug for 〉 6 months maintain higher QoL scores over time. Disease (IPSS, IPSS-R, hemoglobin, transfusion dependence) and patient-related factors (ECOG, gender, comorbidities, disability, frailty) are associated with reduced HRQoL. The prospective assessment of QoL using a validated MDS-specific QoL instrument (QUALMS) and disease course is underway. 1 Buckstein, R., Alibhai, S.M., Lam, A., et al. The health-related quality of life of MDS patients is impaired and most predicted by transfusion dependence, hemoglobin and age. Leukemia Research. May 2011 Vol 35, Supplement 1, Pages S55-56. Disclosures Wells: Alexion Pharmaceuticals, Inc.: Honoraria, Other: Travel Support , Research Funding; Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Geddes:Alexion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zhu:Janssen: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding. Sabloff:Celgene: Membership on an entity's Board of Directors or advisory committees. Keating:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leber:Novartis Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees. Leitch:Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; AbbVie: Research Funding. Yee:Celgene, Novartis, Otsuka: Membership on an entity's Board of Directors or advisory committees; Agensys, Astex, GSK, Onconova, Genentech/Roche: Research Funding. St-Hilaire:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shamy:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Elemary:Roche: Membership on an entity's Board of Directors or advisory committees; Lundbeck: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Delage:Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rockwood:Pfizer: Research Funding; Lundbeck: Membership on an entity's Board of Directors or advisory committees; CHIR: Research Funding; Nova Scotia Health research foundation: Research Funding; Sanofi: Research Funding; Capital Health research support: Research Funding; Canadian consortium on neurodegeneration in aging and nutricia: Membership on an entity's Board of Directors or advisory committees; Alzheimer Society of Canada: Research Funding; Foundation Family Fund: Research Funding. Banerji:Teva: Other: Unrestricted grant received in the past; Gilead: Other: Unrestricted grant received in the past; Abbvie: Other: Unrestricted grant received in the past; Roche: Other: Unrestricted grant received in the past; Janssen: Other: Unrestricted grant received in the past. Buckstein:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background: In the era of chemo-immunotherapy, risk factors associated with survival in patients with diffuse large B-cell lymphoma (DLBCL) are largely limited to biologic characteristics of disease. Laboratory based studies have postulated that statins (through inhibition of the geranylgeranylation pathways) can induce apoptosis in DLBCL cells; pre-clinical data suggests an anti-cancer potential for metformin (through inhibition of cancer cell growth by activation of AMPK and inhibition of mTOR pathways) and cox-2 inhibitors (anti-proliferative effects through blockade of PI3K pathway, inhibition of angiogenesis and proliferation by blocking eicosanoid receptors). To date, these potential in-vitro benefits have not been demonstrated consistently in "real world" studies. Our objective was to assess the impact of medicines with a biologic potential on lymphoma outcome in the era of rituximab. Methods: We performed a retrospective population-based study of adults ≥66 years diagnosed with DLBCL or transformed lymphoma treated in Ontario, Canada. Administrative databases held at ICES were used to assess the impact of select medications on patient outcomes. All patients treated, with curative intent, with a rituximab containing regimen between January 2005 and December 2015 were included. A 1-year lookback of medication exposure prior to commencing rituximab was used. Cox regression analyses were performed to determine the relationship between medication exposure and lymphoma outcomes. Additional analyses were completed to control for known confounders of survival, including the number of comorbid conditions. Results: A total cohort of 4913 patients were treated with a rituximab containing regimen, most frequently R-CHOP, during the study timeframe. Median age was 75 years (IQR 70-80); 51% were male. The median number of cycles of chemotherapy was 6 (IQR 3-6). The median number of comorbidities was 11 (IQR 9-14). Sixty-nine percent had a high comorbidity score (≥10); 26.4% moderate (6-9); and 4.7% low (0-5). Where mortality data was available, 52.1% of the cohort died at a median of 1 year, of whom 67% died due to DLBCL. In the year prior to commencing lymphoma therapy 45.7% received statin therapy; 16.3% metformin; and 25.0% cox-2 inhibitor. In the univariate analysis, statin exposure (HR 0.88; 0.8 - 0.97) was associated with improved survival, but exposure to cox-2 inhibitor (HR 0.82; 0.65 - 1.04) and metformin (HR 1.11; 0.98 - 1.26) had a no impact, during this timeframe. Adjusting for time varying exposure and demographic variables including socio-economic factors and comorbidities, we demonstrated that additional exposure to statin and cox-2 inhibitors in the 365 days prior to commencing lymphoma therapy was associated with a survival advantage, when compared to those who were never exposed. Statin exposure for 30 days (HR 0.97 [0.96-0.98]), 180 days (HR 0.84 [0.80-0.89]) and 365 days (HR 0.71 [0.63-0.79]) and cox-2 inhibitor exposure for 30 days (HR 0.95 [0.95-0.98]), 180 days (HR 0.76 [0.66-0.86]) and 365 days (HR 0.57 [0.43-0.74]) were independently associated with improved survival. In contrast metformin exposure had no impact on survival in this cohort. Patients with moderate (HR 1.69; 1.25 - 2.29) and high comorbidity scores (HR 3.16; 2.36 - 4.21) had significantly higher risk of mortality (p

Description: Despite advances in treatment for diffuse large B cell lymphoma (DLBCL), approximately one third of patients will relapse, with known risk factors largely limited to the biology of the disease. Recently, patient selection bias has been highlighted as a concern in patients enrolled in DLBCL trials, as the need to categorize patients by cell-of-origin necessitates a prolonged screening period that might exclude patients with a need for urgent treatment and thus more aggressive biology (Maurer et al., JCO 2018). Whether an abbreviated diagnosis to treatment interval represents a surrogate for more aggressive disease and adverse prognosis is unclear in a "real-world" setting. We evaluated the time from diagnosis to treatment (and other pre-treatment time intervals) and additional socioeconomic and system-based variables and their impact on lymphoma outcomes. Methods : Using population-based health administrative databases held at the Institute of Clinical and Evaluative Sciences, Ontario, Canada, we identified adults ≥18 years with DLBCL or transformed lymphoma. We explored the impact of timelines prior to commencing treatment and socio-economic status, distance to treating hospital, inpatient/outpatient status, and type of treatment centre on overall survival (OS) and progression-free survival (PFS). Patients were followed from index (first rituximab treatment) until death, occurrence of a new primary cancer, or March 31, 2017. Cox regression analyses were completed to evaluate the impact of predictor variables on OS. Results: In the population evaluated (n=9446), the median age was 66 years and 54% were of male gender. Forty-four percent were from the top two income quintiles and 86% from urban settings. Educational attainment was evenly distributed. Median number of co-morbidities using the John Hopkins aggregated diagnostic groups (ADGs) was 11 (IQR 9-14) with 61% of patients having a high AGD score (≥10). Patients waited a median of 37 days from diagnosis to treatment (IQR 39), with 25% waiting 〉 60 days. From diagnosis, patients waited a median of 19 days to see a hematologist/oncologist (diagnosis to consult time; IQR 24), followed by a further 15 days before chemotherapy was initiated (consult to treatment time; IQR 22). The first cycle was delivered as an inpatient in 4%. Median number of cycles was 6 (IQR 2) with 61% of patients completing ≥ 6. Most patients lived within 20 km of the treating centre (64%); however, 13% travelled 〉 60 km. At the conclusion of study follow-up, 57% of the cohort were alive with median OS not yet reached (Figure 1). Of the 3499 patients with the cause of death available, 73% had DLBCL listed as primary cause with 9.3% of patients dying on active treatment. In Cox regression analysis, an extended time from diagnosis to treatment was associated with improvement in overall survival. Compared to patients who required treatment within 30 days of diagnosis, patients who were treated within 30 - 60 days of diagnosis (HR 0.72; CI 95% 0.67 - 0.78) and 〉 60 days from diagnosis (HR 0.78; CI 95% 0.71 - 0.85) experienced improved survival (Figure 2). Compared to patients who lived close to the initial treatment centre (〈 20 km), the survival of those patients who travelled more significant distances (〉 60 km was not meaningfully impacted (HR 0.91; CI 95% 0.82-1.01). Conclusion:An abbreviated diagnosis to treatment time in newly-diagnosed DLBCL predicts for inferior overall survival in a "real-world" setting, and is potentially reflective of more aggressive disease biology or clinical behaviour. Clinical trials that require extended screening periods may be inadvertently enriched with patients with lymphomas that exhibit less aggressive clinical behaviour (and improved prognosis). In daily practice, patients with less clinically aggressive presentations should be reassured that their outcome should not be adversely impacted by a reasonable wait time. Forthcoming multivariable analyses will be presented to evaluate the impact of additional socioeconomic and system based variables on survival. Disclosures Buckstein: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.