Background: CLL pts who are ineligible for treatment due to age or with major comorbidities and pts who relapse after initial therapy represent significant unmet needs for this disease. To better understand these populations, we examined the prevalence, treatments, outcomes, and costs for pts who might be considered unfit for chemotherapy and, among unfit treated pts, those who showed evidence of relapse after initial therapy. Methods: The Truven Health MarketScan Database was used to identify pts with newly diagnosed CLL in 2004-2013 using ICD-9-CM diagnosis codes. Pts were defined as unfit for chemotherapy if their age was ≥ 80 or had evidence of major comorbidity. Unfit and relapsed (U/R) pts were defined as having ≥ 2 lines of antineoplastic therapy where the 2^ndline represented a change in therapy. Pts were followed from the index date until end of enrollment or death. Reimbursements were adjusted to 2013 dollars. Results: Of a total of 80,096 pts with CLL, 18,776 met the unfit criteria; and 1,109 pts met the U/R criteria. Unfit pts were 57% male, mean age of 69 (SD 18), and had a Charlson comorbidity score (CCI) of 2.4 (SD 2.0). Comorbidities at diagnosis: lipometabolic disorders (37%), hypertension (37%), diabetes mellitus (20%), chronic pulmonary disease (17%), congestive heart failure (7%), renal disease (7%). U/R pts were 63% male, mean age of 63 (SD 20), and had a CCI score of 3.4 (SD 2.2). Mean survival times for unfit and U/R pts were 26.7 (SD 23.8) months and 21.8 (SD 20.2) months, respectively. Among U/R pts, the most common 1st-line regimens were rituximab (R) ± prednisone(P)/ dexamethasone (D) (24.0%), R + bendamustine ± P/D (9.6%), and R + cyclophosphamide + fludarabine ± P/D (7.2%). Among U/R pts, per patient per month total costs by 1st and 2nd lines of therapies were $15,907 (SD $19,893) and $18,506 (SD $36,977) respectively. Conclusions: The most commonly used regimens for U/R CLL pts included rituximab. Survival for U/R after therapy is modestly lower than for those who might be considered unfit at diagnosis, suggesting that some who might otherwise be considered unfit can benefit from therapy. Medical costs were substantial for this cohort of pts.