An Evaluation of Health Care Utilization, Risk of Infection and Bleeding Among MDS Patients During Periods of Transfusion Dependence or Independence with or without Lenalidomide Therapy

A goal of therapy with lenalidomide (LEN) for MDS pts is hematologic improvement, commonly an erythroid response, which results in transfusion independence (TI). However, it is possible that LEN impacts other non-anemia manifestations of MDS, such as significant bleeding (defined as GI, intracranial, hospitalized bleeds, and bleeding deaths), infections. This retrospective claims analysis examined the occurrence of these events as well as health care utilization (ER visits and hospitalizations), for pts with MDS during periods of transfusion dependence (TD) without active therapy compared to periods of TI with or without LEN.

Claims data from a US national commercial health plan were retrospectively reviewed to assess the impact of TD and therapy with LEN on common medical events. Pts ≥ 18 yrs with ≥ 1 claim for MDS (ICD-9-CM diagnosis codes 238.72–238.75) between 01 Jan 07 and 31 Dec 09 were assessed using the 1^st MDS diagnosis date as the index date. Continuous enrollment in a commercial or Medicare Advantage plan with a medical and pharmacy benefit for 6 mos before the index date (baseline period) and for a variable period after the index date (follow-up period) was required. Four unique cohorts of pt follow up were identified to analyze pt outcomes. Three groups of TI periods were examined: periods not on any active therapy ‘watch and wait’ (A) periods on any length of LEN therapy (B) and long periods on LEN therapy (> 3 refills) (C) as 90% of responding pts do so after 3 cycles. In addition, TD periods on no active therapy (D) were assessed. The dose of LEN administered varied across pts and time periods analyzed. Common medical events of infection, bleeding, ER visits and hospitalizations were evaluated within each period type. TD was defined as ≥ 2 RBC transfusions in 8 wks and TI as pts on <2 transfusions in 8 weeks. Because length of each time period varied, results are presented as incidence rate per person-year to allow comparison across cohorts adjusting for variable exposure time.

A total of 3, 574 pts with MDS were categorized on the basis of transfusions and LEN use resulting in 3, 608 observation periods analyzed. Each pt could account for multiple periods. Average age was 66 yrs and 51% were male. TD periods were associated with the highest incidence of infection and bleeding events compared to any of the TI periods (A, B, or C). In addition hospitalizations and ER visits were highest for TD periods compared to any of the TI periods. Interestingly, the incidence of events during TI periods on longer courses of LEN (≥ 3 LEN cycles) (C) approached that of periods of TI without active therapy (watch and wait) (A).

This retrospective database analysis highlights the possible impact of LEN on 2 important clinical manifestations of MDS. As expected, the incidence of infection and clinically significant bleeding was greatest during TD periods. However, the incidence of these events in TI on LEN for > 3 cycles approached that of TI pts not requiring medical therapy (watch and wait) and highlights a potential broader impact of LEN therapy. The effect of LEN in inducing erythroid response in pts with MDS, especially with the 5q- karyotype, is well established; however, these results indicate LEN may also impact the underlying biology of MDS as seen by a lower incidence of infection and clinically significant bleeds during TI periods on LEN (B, C). Furthermore, these data support the concept that effective therapy periods on LEN are not associated with higher rates of medical events and LEN therapy should be considered for eligible TD pts.

Smith:Celgene: Consultancy; Genzyme: Consultancy; Incyte: Consultancy; Infinity: Consultancy; Merck-Serono: Research Funding; Synta: Research Funding; Celator: Research Funding; Calistoga: Research Funding; BMS: Research Funding; Novartis: Research Funding. Mahmoud:Celgene: Employment. Khan:Celgene: Employment.