Willey, Joanne

7046 Background: In CML-CP there is perceived complexity in risk stratification at diagnosis, and in testing for BCR-ABL kinase domain mutation (KD mut, including T315I) at relapse. We sought to understand AHOP practices in the context of NCCN and European LeukemiaNet guidelines. Methods: Between 2010 and 2012, we studied time dependent practice preferences of n=1,335 AHOP’s using a proprietary, live, case-based market research tool. A core case scenario and variations based on available diagnostic & treatment options were constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of summary respondent selections. All sources of research support were double blinded. AHOP's were presented with a scenario of 59-year old CML-CP patient, then indicated preferred management from up to 9 relevant available/emerging diagnostic or therapeutic options following relapse after 1st-line imatinib. Results: The majority of AHOP’s in 2012 either did not calculate (52%), or were unfamiliar (21%) with Sokal or Hasford risk stratification score. Diagnostic preferences following relapse from 2010-12 are noted in Table (distribution over time, p<0.0001). If T315I was then detected in scenario, we noted marked differences in subsequent treatment preference in 2012 vs. 2011, respectively: decreased AlloBMT (16% vs. 32%); & increased 2nd-line dasatinib (26% vs. 14%) or bosutinib (12% vs. 8%) vs. nilotinib (8% vs. 20%) despite lack of efficacy for each in T315I. Preference increased slightly for ponatinib (16% vs. 14%), but not for omacetaxine (2% vs. 6%). Conclusions: Most AHOP’s do not apply risk stratification. Increasing preference for KD mut panel testing at relapse conforms to guidelines, although not all AHOP’s test. Heterogeneity in T315I treatment suggests uncertainty or unfamiliarity with newer agents, and evidence-based efforts are needed to improve awareness. [Table: see text]

Abstract Abstract 4608 Background: FCR has been a preferred 1st line therapy approach in CLL for the past decade. However it is associated with substantial toxicity and not recommended in NCCN guidelines for patients over age 70. We studied the impact of age, co-morbidities, and tempo of disease on 1st line therapy prescribing preferences of American hematology-oncology physicians (AHOP) for patients with CLL. Methods: During Feb-March 2012, prescribing preferences of 325 individual AHOP were assessed using a proprietary, live, case-based market research tool (Challenging Cases™). A core case scenario was constructed with variations based on altered age, co-morbidities, and tempo of disease progression prior to initial therapy. Preference data were acquired using blinded audience response technology. Responses for each scenario were obtained prior to any display of participant selections. All sources of research support were blinded. Core scenario: 67y male; CD 38+, ZAP 70+, del 13q and del 11q CLL, adenopathy, lymphocytosis, splenomegaly, anemia (Hgb 9.5 gm) but no thrombocytopenia. Co-morbidities: medication-controlled hypertension, moderate restrictive airways disease, and type 2 diabetes managed with metformin. Modified scenario: same clinical presentation except the patient is 72 years of age. Slower tempo of disease scenario: age 68y, time frame of observation without treatment 3 years from diagnosis, now with disease progression, anemia 10.9 gms, FISH only del 13q. Results: A progressive decrease in preference for FCR and commensurate rise in preference for BR as first line therapy occurs as age increases and co-morbidities are present (p<0.001). See table 1 Conclusion: As age crosses the 70 year threshold and as co-morbidities complicate therapy, there is a statistically significant increase in preference among AHOPs for prescribing bendamustine-rituximab as initial management for patients with RAI stage III CLL. Disclosures: Green: Xcenda: Employment; Teva: Consultancy, ownes publically traded shares in Teva Pharmaceuticals through 3rd party investment advisors, ownes publically traded shares in Teva Pharmaceuticals through 3rd party investment advisors Other. Williams:Xcenda: Honoraria. Willey:Xcenda: Employment. Scharf:Xcenda: Employment. Neely:xcenda: Employment. Foran:Xcenda: Honoraria.

Abstract Abstract 3816 Background: The hypomethylating agent (HMA) azacitidine (AZA) significantly improves survival compared to conventional care regimens for patients (pts) with “higher risk” MDS (including both Int-2 & High-Risk according to IPSS) (Lancet Oncol 10:223, 2009 – first presented Dec 2007); a more recent trial of the HMA decitabine (DEC) vs. best supportive care in pts with similar IPSS failed to show a significant survival advantage (JCO 29:1987, 2011 – first presented Dec 2008). Since 2006 the immunomodulatory drug lenalidomide (LEN) has been FDA-approved for treatment of anemia in lower-risk MDS pts & deletion of chromosome 5q (Del5q). However, no phase III survival data have been presented with LEN in patients with higher risk MDS, nor is it an expert consensus 1st-line treatment recommendation in higher risk setting (NCCN Guidelines 2011). We sought to evaluate the change in 1st-line treatment preference with these 3 approved agents for higher risk MDS among AHOP's from 2006–2010 in relation to pertinent survival data as it became available. Methods: Between 2006–10 we studied time dependent prescribing preferences of n=1960 AHOP's in a prospective annual research series. Approx. 330–450 individual AHOP's participated in any given year. AHOP demographic data was available from 2007–10 (n=1510); they were predominantly male (77%), working in Community setting (79% vs. 21% Academic), & in small group practice (≤5 providers −59%, including 18% “solo practice”). All regions were represented (NE 23%; SE 22%; Central 19%; SW 13%; West 23%). Most (57%) were >10yrs out from training, and only 18% were <5yrs out from training. A total sample was studied using an extensively tested, live, case-based, market research vehicle to anonymously acquire data. AHOP's were presented with a scenario of an older pt with higher risk MDS (High-Risk 2006–09; Int-2 in 2010) & specific cytogenetic abnormalities, then indicated their preferred treatment from up to 10 relevant available/emerging 1st-line therapeutic options. In each, the scenario was of a pt age 63 yrs (2006–08) or 68–70 yrs (2009–10); with symptomatic anemia & pancytopenia; no response to darbepoietin; with RAEB-2 - excess Bone Marrow blasts 11% (2006–09) to 16% (2010); complex (2006–09) or normal cytogenetics (2010); and both without and then with Del5q in same scenario (2008–10). The distribution of treatment choices was compared over time & according to Del5q status using a chi-square test. Results are shown in Table below. In NON-Del5q scenario, a clear & significant shift toward greater AZA preference by almost 2-fold (from 40% to 78%) was apparent after 2007 (P<0.0001). For same scenario With Del5q (2008–2010), treatment preferences changed significantly over time (P<0.0001), with lower 1st-line AZA and greater DEC & LEN preference (the latter >40% after 2008). In addition, a marked and significant increase in 1st-line LEN preference was observed when AHOP's were presented with the same higher-risk scenario each yr but With-Del5q vs. NON-Del5q (p<0.0001). For “Non Del 5q” vs. “With Del 5q” scenarios, p-values result from a chi-square test, testing for any difference in the distribution of treatment choices over time. *(p<0.0001) - LEN With-Del5q vs. NON-Del5q in higher-risk scenario each year, 2008–2010. Conclusions: Significant changes in 1st-line treatment preferences of AHOPs for pts with higher-risk MDS are apparent in the findings from 2008–10, the time frame following the availability of randomized phase III data demonstrating a survival advantage for AZA therapy. When the presence of a Del5q abnormality is added to the same higher-risk scenario, treatment preferences change dramatically with a significantly increased preference for LEN (despite no available ph III survival data supporting this approach) and for DEC (despite a “negative” ph III trial). These findings suggest important educational gaps concerning the available phase III survival data supporting first line prescribing preferences for patients with higher risk MDS. Efforts to address this gap via evidence-based approaches are warranted. Disclosures: Foran: Celgene: Honoraria; Xcenda: Honoraria. Williams:Xcenda: Honoraria; Celgene: Consultancy, Honoraria, Independent DSMB member, Research Funding. Willey:Xcenda: Employment; Celgene: Business relationship; Eisai: Business relationship. Green:Xcenda: Employment; Celgene: Business relationship; independent DSMB; Eisai: Business relationship.