OBJECTIVES: While persistence with drug therapy is essential to achieve optimal patient benefits, poorly controlled MM results in earlier disease progression, disease-related complications, deleteriously impacts quality of life, and ultimately death.  This study assesses the relationship between treatment LEN adherence/persistence and indicators of lack of disease control and disease-related complications of MM. METHODS: Commercial and Medicare Advantage enrollees initiating LEN for treatment of MM with pharmacy and medical benefits in the 6 months prior and 1 year following initiation of LEN were identified in a US health plan claims database (7/1/2007-6/30/2011).  Persistence was defined as days from the first LEN treatment to the earlier of either the date of discontinuation or end of the follow-up period.  Adherence was measured by the medication possession ratio. Indicators of disease control included in this study were inpatient hospitalization(s) and number of ER visits.  Disease-related complications included evidence of skeletal-related events (SREs) defined as fracture, spinal cord compression, or radiation to the bone; and sepsis. RESULTS: Among the 605 patients meeting the inclusion criteria, persistency with lenalidomide averaged 6.0 months (median = 4.9) with  57.9% of patients being persistent for the entire year.  A one month increase in persistence was associated with a lower probability of SREs (OR=0.96; p=0.078), sepsis (OR=0.86; p<0.001), and relapse or disease progression (OR=0.78; p<0.001).  The probability of an inpatient hospitalization (OR=0.68; p-value<0.001) and additional ER visits (OR=0.83; p=0.002) were both lower with better persistence.  A higher medication possession ratio measured in year 1 was associated with increased overall survival (p=0.007). CONCLUSIONS: This analysis demonstrates that continuous treatment with LEN  improves disease control in MM patients, as well as  reduces health care utilization and related costs as indicated by the lower risk of hospitalizations and fewer  ER visits.