Survival of Patients with Del(5q) Syndrome in the Lenalidomide Era

Abstract Background: Myelodysplastic syndrome with deletion 5q [del(5q) MDS] is characterized by higher incidence in older women, progressive anemia, and >70% rate of hematologic response to single-agent lenalidomide (Len). Len was approved for del(5q) MDS by the United States Food and Drug Administration (FDA) in 2005 on the basis of response rates, with uncertain effect on overall survival (OS). Our objective was to evaluate whether the availability of Len affected the frequency of del(5q) designation among newly diagnosed MDS cases in the US, and to compare OS of del(5q) MDS patients treated with upfront Len or with hypomethylating agents (HMA, azacitidine or decitabine), which were an alternative therapy for MDS available in the US. Methods: We selected cases of low-grade MDS diagnosed in 2001-2011 from the linked Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) data base. Patients were >65 years of age at diagnosis. We identified treatment with Len or HMA in the subpopulation of del(5q) cases diagnosed in 2007-2011 who had complete records of injectable and oral chemotherapy drugs (i.e. with Medicare Part D coverage). Transfusion dependence was assessed by identifying all transfusions within 3 months before therapy, and in months 1-2, 3-4, or 5-6 after treatment initiation. We compared overall survival (OS) using log-rank tests, and in multivariable Cox models adjusting for available confounders, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 21,384 low-grade MDS patients, the frequency of del(5q) MDS designation (N=655) doubled after approval of Len (2% in 2001-06 vs. 4% in 2007-11, P We compared outcomes of del(5q) MDS patients from 2007-2011 (N=157) who had complete record of oral prescriptions (i.e. enrollees in a Medicare Part D plan), including 114 patients treated with upfront Len and 43 treated with upfront HMA. Patients treated with Len were on average older (median age 81 years for Len vs. 78 for HMA, P=.007), more often female (75% vs. 51%, P=.007), with poor functional status (16% vs. 2%, P=.026) or with Medicaid co-insurance (24% vs. 9%, P=.046). There was no significant difference in time from diagnosis to treatment (median 3 months, P=.10), comorbidity index (P=.22), prior hospitalization (P=1.0) or prior transfusions (P=1.00). However, HMA-treated cases had a higher prevalence of pre-treatment G-CSF use (21% vs. 4%, P=.003) and more frequently a subsequent record of acute leukemia (12% vs. 2%, P=.017). OS was significantly better among patients treated with Len than with HMA (median 2.8 vs. 0.9 years, Fig. A), and remained so in a multivariable model adjusting for age, sex, race, baseline transfusion dependence, prior G-CSF, hospitalization, and poor functional status (adjusted HR, 0.27, CI, 0.16-0.43, P Conclusions:In this first population-based assessment of survival outcomes among US patients with del(5q) MDS, the FDA approval of Len led to an increased designation of del(5q) among MDS cases, which will confound studies relying on historical cohort comparisons. Rates of transfusion independence after Len in del(5q) MDS were similar to experience from clinical trials. A significant proportion of del(5q) MDS patients do not receive Len, and state-subsidized co-insurance was associated with improved access to this expensive drug. Among del(5q) MDS patients who receive active therapy, upfront Len is associated with a significantly better OS and a higher rate of transfusion independence than upfront HMA. Download : Download high-res image (134KB) Download : Download full-size image Disclosures Reagan: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria. Olszewski: TG Therapeutics: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Consultancy.