Treatment of Higher-Risk Myelodysplastic Syndrome (MDS) by American Hematology-Oncology Providers (AHOP's): Changes in 1st-Line Treatment Preferences Over Time in Relation to Cytogenetics & Survival Data From Randomized Studies (2006–2010),
Authors: Foran James M. , Heckman Michael G. , Williams Michael E. , Willey Joanne , Green Mark R. 
Published: October 2019

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.