High-Risk Myelodysplastic Syndrome: First-Line Treatment Choices Often Not Supported by Evidence

Caroline Helwick

March 2012, Vol 3, No 2 - ASH Annual Meeting


A review of treatment patterns for higher-risk myelodysplastic syndrome (MDS) shows growing use of lenalidomide, despite the lack of phase 3 survival data supporting this approach, according to research conducted at the Mayo Clinic Flori da, Jacksonville, in collaboration with Xcen da, a research and consulting firm. Since 2006, lenalidomide has been approved for the treatment of anemia in lower-risk patients with MDS and deletion of chromosome 5q (del[5q]). However, no phase 3 survival data have been presented with lenalidomide in patients with higher-risk MDS, nor is it an expert consensus first-line treatment recommendation in the higher-risk setting, James M. Foran, MD, of the Mayo Clinic Florida, pointed out. The hypomethylating agents azacitidine and decitabine are both approved for higher-risk MDS. Azacitidine has shown a survival advantage compared with conventional-care regimens where-as decitabine, versus best supportive care, has not.

"In view of the availability of these 3 FDA [US Food and Drug Administration]-approved agents, we sought to evaluate the change in first-line treatment preference for higher-risk MDS among American hematologyoncology providers from 2006 to 2010 in relation to pertinent survival data as they became available," Dr Foran said. The analysis included 1960 providers who took part in a prospective annual research series. The physicians were presented with a scenario of an older patient with higher-risk MDS and specific cytogenetic abnormalities; they then indicated their preferred treatment from up to 10 relevant available or emerging first-line options.

In the non-del(5q) scenario (2006- 2010), a clear and significant shift toward greater azacitidine preference was apparent, from 40% in 2007 to 78% in 2010. There were declines in the use of both decitabine and lenalidomide over time. For the same scenario with del(5q), treatment preferences also changed significantly over time (2008-2010), with decitabine use declining and azacitidine and lenalidomide use increasing. In 2010, decitabine was preferred by 11% of physicians; 42% preferred azacitidine and 42% preferred lenalidomide.

"Significant changes in first-line treatment preferences among providers for patients with higher-risk MDS are demonstrated in this prospectively acquired 5-year database. Between 2008 and 2010, an increasing divergence in preferences for azacitidine rather than decitabine as first-line therapy in patients with non-del(5q) higher-risk MDS is evident. When the presence of a abnormality is added to the same higher-risk scenario, treatment preferences during the same 3-year interval are markedly different, with a significantly increased preference for lenalidomide, despite no available phase 3 survival data supporting this approach," Dr Foran said. "These findings suggest there are important educational gaps concerning the available phase 3 survival data supporting first-line prescribing preferences for patients with higher-risk MDS, and efforts to address this gap via evidence-based approaches are warranted."