Lenalidomide Performance in the Real World: Patterns of Utilization and Effectiveness in a Medicare Population with Myelodysplastic Syndromes

Lenalidomide (LEN) was approved in the U.S. in December, 2005 for patients (pts) with transfusion-dependent (TD) anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with a deletion 5q (del5q). In this patient population, Phase 2 clinical trial evidence indicates that 2/3 of TD pts achieved transfusion independence (TI), with 90% of pts achieving transfusion benefit by 3 months. This observational study examines LEN treatment patterns and association with reduced transfusion needs in a Medicare-enrolled population with MDS.

MDS pts from 2006–8were identified using ICD-9 CM codes from 100% Medicare claims. Claims data from 2005–2008 were linked to Medicare enrollment files, and zip code-level measures of income and education from the 2000 U.S. Census. The study cohort consisted of MDS pts enrolled in Medicare Parts A and B and without Medicare Advantage (HMO enrollment) from 12 months before MDS diagnosis, and enrolled in Part D from diagnosis forward, allowing for observation of oral drug use. Patients were followed until death or end of study. LEN use was identified from Part D event files based on National Drug Code. Claims data were used to calculate duration, daily dose, time to initiation of treatment, and relationship to erythropoiesis-stimulating agents (ESAs) and hypomethylating agents (HMAs) use. Transfusion status was evaluated each week (wk), based on receipt of transfusions during the current and preceding 7-wk period (rolling). TD required transfusions during 2 of the 8 wks, separated by at least 3 wks. TI required a period of 8 wks without transfusions. An intermediate transfusion user (TU) category received 1 transfusion during the prior 8 wks. Change in transfusion status during a treatment episode was examined. Bivariate analyses examined sample means and proportions, overall and by MDS risk group defined based on initial diagnostic codes.

The cohort of 22,480 pts was predominantly white (88%) and female (58%), and 76% were age 75 years or older. MDS risk group was ICD-9 coded as 456 (2%) del5q, 5,989 (27%) other lower-risk, 1,277 (6%) higher-risk and 14,758 (75%) not otherwise specified (NOS). LEN use rates were 3% (n=716) overall, with 31% of del5q, 3% of other lower-risk, 5% of higher-risk and 2% of MDS NOS receiving therapy. Median time to initiate LEN (11.5 wks, range 0–132) was less for del5q (8 wks) than for other lower-risk coded patients (20 wks); most (86%) del5q pts and nearly all other lower-risk pts (96%) received ESAs prior to LEN. Pts received a mean of 4.1 4-wk cycles of LEN (median=2); 53% received <3 cycles. Multivariate analysis indicated that LEN initiation was negatively associated with older age, poor performance status, and baseline diabetes, stroke, and renal disease, and positively associated with del5q risk group and baseline pancytopenia and thrombocytopenia.

At LEN initiation 36% were TI, 31% TU and 33% TD. Point estimates indicate that 44% of pts who were either TU or TD at LEN initiation (53% of del5q) experienced a reduction in transfusion use. Among those TD at LEN initiation, 45% reduced transfusion use during treatment, while 15% achieved TI. 43% of pts TU at LEN initiation achieved TI status. When limited to patients with ≥3 cycles, 71% of pts who were TU or TD at LEN initiation (83% of del5q) experienced reduced transfusion use. 77% of TD patients reduced transfusion use during treatment, and 40% achieved TI. Finally among these patients who were TU at LEN initiation, 67% became TI. Small sample sizes provided inadequate power to detect differences between MDS risk groups.

This large population-based observational study of LEN use in Medicare-enrolled MDS pts showed that use rates were highest among del5q pts, as expected. Older pts were less likely than younger pts to receive LEN treatment. Shorter time to initiation of LEN for del5q vs. lower-risk pts indicates that physicians more promptly prescribe LEN for those with del5q. Response rates for the full cohort reflected the mix of risk groups and relatively short duration of therapy for many pts, but overall were consistent with published clinical trials. Response rates were higher when at least 3 cycles of therapy were received, underscoring the need to sustain therapy to achieve therapeutic response.

Gore:Celgene Corporation: Consultancy, Research Funding. Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding. Mahmoud:celgene: Employment. Davidoff:Novartis: Research Funding; Celgene: Equity Ownership, Research Funding; National Institutes of Health: Research Funding; GlaxoSmithKline: Research Funding.