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Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world, accounting for approximately 30% of adult leukemias. The majority of CLL patients are elderly and have co-existing medical conditions. This limits therapeutic options and precludes many from receiving the recognized standard of care regimen, fludarabine, cyclophosphamide and rituximab (FCR). A number of recent studies have evaluated alternative chemoimmunotherapies for these patients. The objective of this study was to describe patient characteristics, treatment patterns, and resource utilization for patients who are unfit for a standard fludarabine-based regimen as first-line treatment for CLL in Spain, Italy, and the UK. A retrospective chart review was undertaken at 18 sites in Spain, 16 in Italy, and 17 in the UK, to identify CLL patients who initiated treatment between January 2011 and December 2012, with a target sample size of 150 per country. Eligible patients were defined as those who initiated first-line CLL treatment that did not include fludarabine (UK and Spain) or standard-dose fludarabine (Italy) which ensured that elderly patients with comorbidities were included. The variability in definitions was due to increased use of reduced-dose fludarabine regimens in Italy for patients not otherwise suitable for a standard dose of fludarabine. Data on demographic and disease-related characteristics, treatment patterns, and health resource utilization were abstracted from diagnosis until December 2013. Among eligible patients (Spain, n=127, Italy, n=121, UK, n=94), the mean age at treatment initiation was 75.9, 73.8, and 76.8 years, respectively. In the UK, 89.4% had 2 or more comorbidities compared to 74.8% in Spain and 65.3% in Italy. In all countries, chlorambucil monotherapy was the single most common regimen, prescribed to 59.6% of patients in the UK, 38.6% in Spain, and 30.6% in Italy. Bendamustine plus rituximab was the next most common regimen in the UK (17.0%) and Italy (23.1%). In Spain, the second-most common regimen was chlorambucil plus rituximab (18.9%). In Italy, 9.9% of patients received the reduced-dose fludarabine regimen, FCR-Lite. In both Spain and the UK, 40% of patients were hospitalized during the follow-up period, compared to 27% in Italy. Emergency room use ranged from 2% in the UK to 40% in Spain. A large majority of patients in all countries utilized outpatient services and laboratory monitoring, with more frequent of visits in Spain and Italy relative to the UK. Hospitalization costs were the largest cost driver (€3284 in Spain, €1312 in Italy, €10291 in the UK). Observed differences in hospital costs across countries were due to variation in: the proportion of individuals being hospitalized, with hospitalizations less common in Italy; length of hospital stay, with a minority of long and costly hospital stays in the UK; and hospital per diem costs. In Spain, outpatient visits comprised the second largest category of costs, while in Italy the second largest category was laboratory tests. In the UK, the second largest category was hospice care, although this was heavily influenced by a small number of individuals with very lengthy hospice stays. For the majority of UK patients, outpatient care was the second-highest category of costs. In conclusion, CLL patients who initiated first-line therapy during 2011 and 2012, with a regimen that did not include fludarabine (UK and Spain) or did not contain standard-dose fludarabine (Italy), were elderly, with 2 or more comorbidities. The most frequently administered treatment was chlorambucil monotherapy. Resource utilization patterns varied across countries; while some differences may have resulted from differences in patient and disease characteristics, they likely also reflect variation in management strategies between these countries. These results provide valuable baseline data to understand the potential impact of future treatments for this patient population. Abstract 2646. Table 1.SpainItalyUK% with utilizationMean annual cost per patient (€)% with utilizationMean annual cost per patient (€)% with utilizationMean annual cost per patient (€)Hospitalization40.5328426.9131240.410291Hospice008.42055.36380Emergency room40.311515.01072.24Laboratory95.052899.052687.178Outpatient95.0116794.021968.8874Transfusions25.25117.04330.1226 Disclosures Delgado: Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria; Celgene: Honoraria; Novartis: Consultancy, Honoraria. Rossi:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Raine:GSK: Employment. Haiderali:GSK: Employment.

Introduction: A systematic review of clinical trials investigating interventions used for the first-line treatment of patients with CLL who are not eligible for fludarabine-based therapy was undertaken and the feasibility of performing an adjusted indirect comparison (AIC) for OChl versus B, GA101Chl and RChl was explored. Methods: Trials were identified by a systematic review; details of the methodology can be found in abstract B1333 of Hematologica (Woods et al, 2013). The trial designs, patient populations and treatment doses were examined to identify any evident systematic differences among the trials that might be expected to result in heterogeneity. The feasibility of performing an AIC using conventional methods and also alternative methods such as matching-adjusted indirect comparison (MAIC) was evaluated. Results: The trial evidence network is presented in Figure 1. Figure 1. Evidence Network Figure 1. Evidence Network The following trials were examined in detail to assess the feasibility of conducting an AIC with Chl as the common comparator. µ COMPLEMENT-1 comparing OChl with Chl (Hillmen et al., 2013). µ Knauf et al (2009; 2010, 2012) comparing B with Chl µ CLL11 comparing RChl and GA101Chl with Chl (Goede et al., 2014). Differences were found between studies in terms of treatment regimens, study design, subject characteristics and study endpoints. There were substantial differences in the actual median total dose of Chl monotherapy received by each patient, ranging from 728 mg in COMPLEMENT-1 through 522 mg for Knauf et al. to 384 mg in CLL11. Patient inclusion and exclusion criteria differed among trials, including disease stage (no Stage A patients in Knauf et al), absence or presence of criteria for fitness for fludarabine therapy, as determined by age or co-morbidity measurements such as the Cumulative Illness Rating Scale (CIRS) scores. The COMPLEMENT-1 population was older than that studied by Knauf et al. but younger than the population in the CLL11 trial. The majority of patients had ECOG Performance Status (PS) 1 in the COMPLEMENT-1 trial but PS 0 in the Knauf et al., trial. The definitions of response also varied among trials with COMPLEMENT-1 and CLL11 using the 2008 NCI-WG criteria and Knauf et al. using the earlier 1996 criteria. Discussion: Naïve indirect comparisons are subject to a variety of confounding factors which may bias the estimates in an unpredictable direction with uncertain magnitude. There are a large number of differences between the identified trials which make adjustments for heterogeneity difficult. Different Chl monotherapy regimens have shown differing efficacy (Catovsky et al., 2011) and, there is no available evidence which might be used to calculate the magnitude of this effect. Methods such as MAIC and predictive models may overcome some of the heterogeneity between clinical trials and in some cases allow for comparisons of treatments in the absence of a common comparator. Within this set of studies, there was an insufficient set of matching variables to enable for matching and validation of the match with other variables and/or a common comparator arm. Furthermore, although these methods may account for differences in patient characteristics, they cannot adjust for other differences, such as the definition or ascertainment of endpoints. Conclusions: To avoid bias, any indirect comparison of these interventions should adequately account for heterogeneity within the evidence network, with careful consideration of the factors identified in this review. The effectiveness of these interventions in comparison to Chl in routine clinical practice may differ from the efficacy observed in the trials, particularly where the Chl regimen used in routine practice differs from that investigated in the trials. Disclosures Wolowacz: GlaxoSmithKline. Sorrel Wolowacz is a full-time employee of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study: Research Funding. Mitchell:GlaxoSmithKline. Sarah Mitchell is a full-time employee of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study: Research Funding. Haiderali:GSK: Employment.