ALBERT

Description: Abstract 1012 Poster Board I-34 Background: Disparities in survival between black and white patients (pts) exist for many malignancies, including AML. Potential causes include differential access to care; variable aggressiveness of therapy; and biological heterogeneity. Black men with AML have lower complete remission (CR) and overall survival (OS) rates than black women and whites, as shown in a previous Cancer and Leukemia Group B (CALGB) study in which induction therapies were defined, but subsequent treatment compliance and intensity was unknown. We investigated whether differences in post-remission therapy (PRT) might explain disparity in outcome. Methods: All pts with newly diagnosed AML treated with cytarabine-based induction therapy between 1997 and 2008 were included. PRT was defined as either cytarabine-based chemotherapy or bone marrow transplant (autologous or allogeneic) administered to pts achieving a CR and prior to relapse or in the setting of no relapse. PRT was coded according to intensity, in cumulative mg/m2 of cytarabine or mitoxantrone received, with BMT assigned the highest intensity of cytarabine. Data on known prognostic factors (age, white blood cell count (WBC) at diagnosis, pathologic subtype, AML etiology, cytogenetic risk groups (as defined by CALGB 8461)) were collected and controlled for in multivariable analyses. Time to PRT was measured in days from date of discharge after induction chemotherapy to date of PRT initiation, excluding patients with time to PRT 〉150 days, considered too long to be true consolidation. Comparisons between black and white pts were performed using linear, logistic, and proportional hazard regressions, exploring intensity of and time to PRT, and number of PRT cycles, along with potential interaction terms, controlling for known prognostic factors for outcome. Results: Of 460 pts, 421 had adequate data on PRT. Of these, 379 (90%) were white, 32 (8%) black, 10 (2%) other, and 46% were female. Similar to CALGB data, and compared to whites, blacks were younger (mean age 53.5 vs. 57.5 years, p=.11), had a higher proportion of favorable (18.8% vs. 12.7%) and poor risk (34.4% vs. 24.5%) cytogenetics (p=.28), and were less likely to attain a complete remission (CR, 66% vs. 73%, p=.39), though differences did not reach significance due to sample size. Other baseline characteristics, including reinduction rates, were similar. The 236 pts who received PRT included 18 blacks (56%) and 218 whites (58%, p=.89). In univariate analyses, for blacks vs. whites, median time to PRT initiation was 31 vs. 23 days (p=.33); cytarabine intensity was 66,654 mg/m2 vs. 50,630 mg/m2 (p=.26); and number of cycles was 2.4 vs. 2.1 (p=.41), respectively. Median time to PRT among all men was 24 days, compared to 21 days for all women (p=.09), and for pts =60 years (p=.43). Median survival was 0.72 years in both black and white patients (p=.57). Among those receiving PRT, median survival was 3 years in blacks and 1.4 years in whites (p =.22); for pts not receiving PRT, median survival was.22 years in blacks and.32 years in whites (p =.25). In multivariate analyses, time to PRT was shorter for whites (HR=.25, p=.016), particularly when white men were compared to black men (HR=.12, p=.012), whereas no differences were found for women. Survival differences did not reach significance; nor was there an interaction for male and black race. Conclusions: Time to PRT is shorter for whites compared to blacks with AML, though cycle dose intensity and number are similar. Despite this, overall survival was not different between blacks and whites receiving PRT. In the post-remission setting, blacks and whites appear to receive similar chemotherapy management, and thus differential treatment aggressiveness and compliance are not explanations for varying outcome between races. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Hospital services can be significantly reduced over the weekend. This was associated with higher mortality among patients with serious medical conditions in previous studies. It is unknown whether weekend admissions affect outcomes of AML patients, as delay in treatment or delay in obtainment of procedures (such as triple-lumen catheter [TLC] placement requisite for anthracycline delivery) may occur for weekend admissions. We investigated quality of care and clinical outcomes of newly-diagnosed AML patients treated with induction chemotherapy and hospitalized on weekends vs. weekdays. Methods: We conducted a retrospective review of all AML patients treated with cytarabinebased induction chemotherapy at Cleveland Clinic from 1994–2008. Data on known prognostic factors (age, WBC at diagnosis, cytogenetic risk groups [as defined by CALGB 8461] and AML etiology [de novo vs. secondary AML]) were collected and controlled for in multivariable analyses. Quality measures included time to TLC placement; time to induction chemotherapy (TTI); length of stay (LOS); early death (within 15 days of chemotherapy initiation); and 30-day mortality. Weekend admissions were defined as starting Friday, 5pm through Monday, 12am. Factors associated with quality of care and outcomes were assessed by the routines of linear, categorical, and survival analyses. Results: In all, 422 patients were identified. Median age was 61 years (range:17–81) and 47% were female. Median baseline WBC was 9.9/mcL (range:0.4–550); 4.7% had acute promyelocytic leukemia, and 30% had secondary AML. Cytogenetics risk distribution was: favorable (11.6%); intermediate (41.2%); adverse (24.2%); unknown/no growth (23%). In all, 24.4% (n=103) were admitted on the weekend. The complete remission (CR) rate was 66.6%; Median times to TLC was 2 days (range:0–27); TTI was 2 days (range:0–22); and LOS was 32 days (4–91). Early death rate was 3.1%, and 30-day mortality 10.4%. Compared to younger (

Description: Abstract 1043 Poster Board I-65 Background: In older (age 3 60) AML patients (pts) who are induced into complete remission, it is unclear whether post-remission therapy provides additional benefit. Methods: We examined all older AML pts treated with cytarabine-based induction chemotherapy at a single institution between 1997 and 2008. Data on known prognostic factors (age, white blood cell count (WBC) at diagnosis, cytogenetic risk groups (as defined by CALGB 8461) and AML etiology (de novo vs. secondary AML)) were collected. Of 240 pts identified, 25 had unknown post-remission status, leaving 215 pts for analyses: 81 receiving cytarabine-based post-remission therapy (PRT) for 1-2 cycles; 134 received no PRT. A cohort study using a propensity score method was conducted in which pts receiving PRT and those not receiving PRT were matched in a 1:1 ratio to address potential sample selection bias and to better balance patient characteristics. A logistic regression was used to predict the propensities of receiving PRT using individual characteristics: age, gender, race, WBC at presentation, AML cytogenetics, secondary AML, re-induction, FAB classification, and complete remission (CR). Overall survival (OS) was measured from the time of diagnosis; disease-free survival (DFS) from the time of CR. Individual characteristics and survival between groups were assessed by the routines of linear, categorical, and survival analyses. Results: Median age was 68 years (range, 60-81). Patients receiving PRT were more likely to be younger (67 vs 69 years, P=.003), male (67% vs. 52%, p=.04), have de novo AML (75% vs. 50%, p=.0012), favorable- or intermediate-risk cytogenetics (65% vs. 36%, p

Description: Background: Patients with myelodysplastic syndrome (MDS) may present with anemia and become red blood cell (RBC) transfusion dependent (TD), which increases the risk of iron overload (IO). Iron chelation therapy (ICT) treats IO and has been shown to be associated with improved survival and quality of life among TD MDS patients. Deferasirox (DFX) is an oral ICT used to reduce IO in TD MDS patients. This study aims to assess real-world treatment patterns and adherence among MDS patients on Medicare receiving DFX as ICT. Methods: This was a retrospective cohort study using 100% Medicare claims data from 2006-2013. Patients were diagnosed with MDS, identified using ICD-9 codes (238.72-238.76), and entered the study cohort when they met a minimum transfusion threshold of either: 10 consecutive weeks with at least 1 unit of RBC transfusion, or 20 total units of RBC transfusions. Treatment patterns, including discontinuation and treatment changes, were assessed among patients who received DFX as initial ICT and who had ≥180 days of follow-up. Discontinuation was defined as a minimum 45-day treatment gap. Adherence was defined as a medication possession ratio (MPR) ≥ 0.8. Treatment discontinuation, overall survival, acute myeloid leukemia (AML)-free survival, and cardiac event-free survival were compared between adherent and non-adherent patients using Kaplan Meier (KM) survival analysis, as well as Cox regressions controlling for time-dependent ICT use and baseline characteristics. Survivals were estimated as time from cohort entry to the event. Results: Among 6,796 MDS patients who met the minimum transfusion threshold, 591 (8.7%) received ICT. Median weeks of ICT was 15.14 (range=2.29 - 201.43 weeks). 583 (98.6%) initiated with DFX, and 374 DFX patients had a follow-up period of ≥180 days. Of these 374 patients, 213 (57.0%) discontinued DFX treatment within 180 days of initiation. Among the remaining 161 patients, one switched to deferoxamine (DFO), none augmented treatment with DFO, and 160 continued on DFX. The KM-estimated 3-month and 1-year DFX discontinuation rates were 36.5% and 77.4%, respectively, and the average time to discontinuation was 84.4 [Standard Deviation [SD]=48.6] days. Overall, the average 6-month MPR was 0.69 (SD=0.30), and 49.1% of patients were adherent (MPR≥0.8). Adherent patients had similar baseline characteristics compared with non-adherent patients, except that a lower proportion had renal disease (24.2% vs. 38.3%, P

Description: Background: The majority of patients with myelodysplastic syndromes (MDS) develop anemia, and may require red blood cell (RBC) transfusions and become transfusion-dependent. Transfusion-dependency places patients at significant risk of developing iron overload. Iron chelation therapy (ICT) has been associated with improved overall and leukemia-free survival among MDS patients with iron overload. This study aims to assess the real-world treatment patterns of ICT among MDS patients, and its associated survival outcomes. Methods: Using 100% Medicare claims data from 2006-2013, this retrospective cohort study included patients diagnosed with MDS, identified using ICD-9 codes (238.72-238.76). Selected patients entered the study cohort when they met a minimum transfusion threshold of either: 10 consecutive weeks with at least 1 unit of RBC transfusion, or 20 total units of RBC transfusions. Patients were classified into ICT and non-ICT cohorts depending on whether ICT was received after meeting the minimum transfusion threshold, and were observed until death or end of follow up in the database. Patient characteristics and clinical outcomes were compared between the ICT and non-ICT cohorts. Overall survival, acute myeloid leukemia (AML)-free survival, and cardiac event-free survival were assessed using Kaplan Meier (KM) survival analysis, as well as Cox regressions controlling for time-dependent ICT use and baseline characteristics. Survivals were estimated from time of cohort entry until the event. Results: 591 (8.7%) of the 6,796 MDS patients who met the minimum transfusion threshold received ICT. Median weeks of ICT was 15.14 (range= 2.29 - 201.43 weeks). The ICT cohort was younger (77 vs. 80 years, P

Description: Patients with low-risk myelodysplastic syndromes (MDS), defined as refractory anemia (RA), RA with ringed sideroblasts (RARS), or International Prognostic Scoring System (IPSS) scores of 0–1.0, are treated with growth factors (GF) or chemotherapy (Chemo) in the setting of transfusion dependence. Predictive models (PM) for response to GF have been developed based on red blood cell (RBC) transfusion needs and erythropoietin (epo) levels, but report no difference in survival among good, intermediate, and poor PM groups (the PM good group has few transfusion needs and a low epo level, while the PM poor group has high transfusion needs and high epo levels: Jadersten et al. Blood2005;106:803). The optimal therapy (chemo vs. GF) based on response rates (RR) and survival has not been defined. Methods: We performed a decision analysis to determine the optimal therapy for low-risk MDS patients. Patients receiving chemo (n=417) or GF (n=382) were identified from a MEDLINE search on the keywords MDS, RA, RARS, treatment, GF, and chemo. Original articles with individual patient characteristics, RA or RARS MDS subtypes, and documented effect of therapy were included. From 1985 to 2005, 137 papers representing 2,301 patients with low-risk MDS were reviewed. Individual data was available on 799 patients. Chemo included differentiating agents, immunomodulators, and non-ablative cytotoxic agents; GF included erythropoietin, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. IPSS was calculated when sufficient data were available. RR were standardized and recalibrated according to the International Working Group (IWG) criteria and included complete response, partial response, and hematologic improvement. Median survival in GF patients derived from the Jadersten et al. study, and was validated with data from GF patients in our database. Survival in chemo patients was determined from the database. Cut-points for which treatment strategy to choose, based on RR and survival, were calculated. Results: Baseline variables for chemo patients included (median (range)): age 65(21–83) years; requiring 2(0–8) units RBC transfusions/month; having an epo level of 279(17–4590). IPSS score was 0–1.0 in 88.3% of patients. GF patients were older (72 years, range 43–87), but with similar transfusion needs, IPSS scores, and epo levels to chemo patients. Overall, patients receiving chemo had a RR of 41.5% and a median survival of 78 months, compared to 46% and 44 months, respectively, for GF patients. Survival and RR differences were not statistically significant. Using the decision model, patients in a PM good response group should receive GF unless chemo can yield a RR at a cut-point of 〉34.1%. Patients in the PM intermediate response group should receive chemo if the RR to chemo is 〉10.6%; and those in the PM poor response group should receive chemo if the RR to chemo is 〉3.2%. RR and median survivals for chemo patients did not differ when they were classified according to the three PM response groups. Conclusions: Based on available survival data, low-risk MDS patients falling into a good response predictive group (low RBC transfusion needs and low epo levels) should be treated with GF unless chemo RR are 〉34.1%. Other low-risk MDS patients should probably be treated with chemo. Additional cost and quality of life data are needed to incorporate into future decision models.