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Venetoclax is a first-in-class targeted therapy option that is an inducer of apoptosis in chronic lymphocytic leukemia (CLL) cells. The open-label phase III CLL14 clinical trial showed that venetoclax combined with obinutuzumab (VEN+O) is superior to obinutuzumab combined with chlorambucil in newly diagnosed patients with CLL. The aim of this study was to assess the health economic value of VEN+O for the frontline treatment of CLL in Canada from a publicly funded healthcare system perspective.A partitioned survival analyses model was developed including three health states: progression free, progressed, and death. A cycle length of 28 days and a time horizon of 10 years was assumed. VEN+O treatment for a fixed duration of 12 months was compared to obinutuzumab combined with chlorambucil, fludarabine plus cyclophosphamide plus rituximab, bendamustine plus rituximab, chlorambucil plus rituximab, ibrutinib, and acalabrutinib. The population in the model included both unfit and overall frontline CLL patients, two subgroups were also assessed (patients with del17p/TP53 mutations and patients without del17p/TP53 mutations). Survival data extrapolated from the CLL14 trial were used to populate the model. Uncertainty was assessed via one-way sensitivity analyses, probabilistic analyses, and scenario analyses.Based on the probabilistic analyses, unfit frontline CLL patients receiving VEN+O were estimated to incur costs of Canadian dollars ($) 217,727 [confidence interval (CI) $170,725, $300,761] (del17p/TP53: $209,102 [CI $159,698, $386,190], non-del17p/TP53: $217,732 [CI $171,232, $299,063]) and accrue 4.96 [CI 4.04, 5.82] quality-adjusted life-years (del17p/TP53: 3.11 [CI 2.00, 4.20], non-del17p/TP53: 5.04 [CI 4.05, 5.92]). Obinutuzumab combined with chlorambucil, bendamustine plus rituximab, chlorambucil plus rituximab, and ibrutinib accrued lower quality-adjusted life-years and higher costs and as such, VEN+O was the dominant treatment option. The full incremental analysis showed that acalabrutinib was more expensive and more efficacious compared with VEN+O with an incremental-cost-effectiveness-ratio of $2,139,180/quality-adjusted life-year versus VEN+O and not a cost-effective option in Canada. Probabilistic analyses show that at a willingness to pay of $50,000/quality-adjusted life-year gained, VEN+O has the greatest probability of being cost effective.VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers.

Introduction: Venetoclax has demonstrated deep responses and sustained progression-free survival and is well tolerated in patients (pts) with previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) in clinical trials. Some early studies provided initial insight of venetoclax utilization in the real-world (RW), but RW evidence focusing on venetoclax effectiveness and safety is still limited. This study assessed venetoclax effectiveness, safety, and treatment patterns in CLL pts treated in clinical practice. Methods: The CLL Collaborative Study of Real-World Evidence (CORE), a large multicenter chart review across 21 institutions in 4 countries, enrolled adult pts who initiated a first line (1L) therapy on/after 01/01/2012 or a new line of therapy (LOT) for R/R CLL/SLL on/after 02/12/2014 (current data cut through 06/08/2020). Clinical responses were abstracted from the medical records as assessed by treating physicians or investigators (iwCLL criteria were provided as reference). Overall response rate (ORR) was calculated as the proportion of pts with complete response (CR) or partial response (PR) out of pts with documented response assessments. Treatment patterns included choice of regimens and sequences, dose interruption, dose reduction, and discontinuation. Treatment discontinuation was defined as ending therapy for any reason(s) other than the completion of planned duration of therapy. Interruption was defined as a gap in the same LOT. All analyses were descriptive. Results: Of the 1231 CLL pts in the CORE data, 155 received venetoclax (21 in 1L and 134 in R/R) and were included in this study. Most of the sample were male (65%) and the median age at venetoclax initiation was 67.5 (range 37-91). For high-risk features among pts with available data, 33% (43/132 pts) had del(17p) or TP53 mutation, 24% (31/131 pts) had complex karyotype (≥ 3 abnormalities), and 77% (61/79 pts) had unmutated IGHV. At venetoclax initiation, 46%, 40%, and 14% of 151 pts with available data had low, medium, and high tumor burden, respectively. Median follow-up time from venetoclax initiation across all lines was 7.0 (0.1-43.1) months. Median number of prior LOT for R/R pts was 2 (1-5); the largest proportion of pts (36%) received venetoclax in 2L followed by 3L (26%). In 1L, venetoclax was most frequently used (62%) in combination (Figure 1), while in R/R setting venetoclax monotherapy was more commonly used (61%) followed by venetoclax + rituximab (25%; Figure 2). Majority of R/R pts (63%) received Bruton's tyrosine kinase inhibitors (BTKi) prior to venetoclax (Figure 2). Response was assessed and documented for 114 pts (74%). Among these, ORR was 75% (CR=40%, PR=35%) overall. Pts ≥65 years old had an ORR of 79% (CR=41%, PR=38%, n=74), and pts Overall, 48% of pts had adverse events (AEs) recorded. Five R/R pts (3.2%) had TLS events (defined by Howard or Cairo-Bishop criteria), of which 3 (1.9%) were clinical. Of the 5 pts, 2 had high tumor burden, and 3 had medium burden. Other AEs of interest include neutropenia (17%), thrombocytopenia (9%), and diarrhea/colitis (5%). Overall, 32% of pts discontinued venetoclax; 13% of all pts discontinued venetoclax due to AEs (primarily neutropenia [n=2] and thrombocytopenia [n=2]), followed by disease progression (8%). Venetoclax interruption rate was 14%, and dose reduction rate was 22% overall. Conclusions: Consistent with trial experiences, venetoclax demonstrates high response rates, including high-risk groups, and a manageable safety profile with low rates of TLS in clinical practice. Despite limitations of RW research, this study provides useful insights into treatment practices with venetoclax. Future research with longer follow-up is warranted to better understand the long-term clinical outcomes associated with venetoclax regimens. Disclosures Zheng: AbbVie: Current Employment. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Roeker:Abbott Laboratories: Other: spouse with minority ownership interest ; American Society of Hematology: Research Funding; AbbVie: Other: spouse with minority ownership interest . Manzoor:AbbVie: Current equity holder in publicly-traded company. Tuncer:AbbVie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy. Ujjani:Gilead/Kite: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy; Atara: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding. Barr:Genentech: Consultancy; Merck: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; Verastem: Consultancy; TG therapeutics: Consultancy, Research Funding; Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding. Brown:Novartis: Consultancy; Nextcea: Consultancy; Octapharma: Consultancy; MEI Pharma: Consultancy; Eli Lilly and Company: Consultancy; Astra-Zeneca: Consultancy; TG Therapeutics: Consultancy; Sunesis: Consultancy; Loxo: Consultancy, Research Funding; Sun: Research Funding; Rigel Pharmaceuticals: Consultancy; Pfizer: Consultancy; Catapult: Consultancy; Dynamo Therapeutics: Consultancy; Pharmacyclics: Consultancy; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Gilead: Consultancy, Research Funding; Genentech: Consultancy; BeiGene: Consultancy; Invectys: Membership on an entity's Board of Directors or advisory committees, Other: DSMC; Janssen: Honoraria; AbbVie: Consultancy; Kite: Consultancy; Juno/Celgene: Consultancy; Verastem: Consultancy, Research Funding; Acerta: Consultancy. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support. Skarbnik:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CLL Society: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy; Beigene: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Verastem: Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bannerji:Regeneron Pharmaceuticals: Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc and Pharmacyclics LLC, an AbbVie Company: Research Funding; Sanofi-Pasteur: Other: Spouse is employee; AbbVie: Research Funding. Eichhorst:BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; Ascentage: Other, Research Funding; ArQule: Consultancy, Other, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other; DTRM: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding. Sharmokh:AbbVie: Current Employment, Current equity holder in publicly-traded company. Jiang:AbbVie: Current Employment, Other: may hold stock or options. Pena:AbbVie: Current Employment, Current equity holder in publicly-traded company. Kamalakar:AbbVie: Current Employment, Other: may hold stock or other options. Emechebe:AbbVie: Current Employment, Current equity holder in publicly-traded company. Pivneva:Novartis: Consultancy, Other: Irina Pivneva is an employee of Analysis Group, Inc which received consultancy fees from Novartis.. Burne:Analysis Group, Inc., which has received consultancy fees from AbbVie: Current Employment. Guerin:Abbvie: Consultancy, Other; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.; Sanofi Genzyme: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.. Davids:Celgene: Consultancy; Research to Practice: Honoraria; AbbVie: Consultancy; Sunesis: Consultancy; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; BeiGene: Consultancy; Novartis: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Adaptive Biotechnologies: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Gilead Sciences: Consultancy; Eli Lilly: Consultancy; Syros Pharmaceuticals: Consultancy; Zentalis: Consultancy; Merck: Consultancy; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding. Mato:AbbVie: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Loxo: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

This study aimed to assess the total cost of care (TCC) and budget impact of introducing 12-month fixed duration venetoclax + obinutuzumab (VEN+G) as first-line treatment for chronic lymphocytic leukemia (CLL) from the perspective of a US health plan with 1,000,000 (1M) members. The 3-year model included the following comparators: fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), obinutuzumab + chlorambucil (GClb), ibrutinib (Ibr), and Ibr+Rituximab/obinutuzumab [Ibr+R/Ibr+G]). TCC included US-specific costs associated with treatment (i.e., drug, administration, and wastage), adverse events, routine care, and monitoring. Dosing and safety data were drawn from clinical trials and US package inserts. Budget impact outcomes were presented on an absolute and per-member per-month (PMPM) basis. Sensitivity analyses explored uncertainty in influential parameters, including scenarios testing the duration of treat-to-progression agents. Over the 3-year time horizon, introducing VEN+G in a 1M-member health plan resulted in total cost savings of $1,550,663 (PMPM − $0.04), compared to a scenario without VEN+G. The fixed 12-month duration of VEN+G contributed to this cost saving by reducing cumulative treatment costs compared with Ibr-based regimens. By year 3, the cumulative difference in TCC of VEN+G compared with Ibr, Ibr+G, and Ibr+R amounted to − $300,942, − $367,001, and − $369,784, respectively. Extensive sensitivity analyses supported the base case findings. Introducing VEN+G among first-line CLL treatments to a US health plan resulted in cost savings compared to a plan with chemoimmunotherapies and Ibr-based therapies only. Economic benefits of VEN+G, a novel agent with fixed treatment duration, coupled with proven clinical benefits should help inform formulary adoption decisions and treatment recommendations.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a significant health and economic burden in the United States. Treatments include chemoimmunotherapy, such as obinutuzumab (G) plus chlorambucil (Clb) or bendamustine plus rituximab (BR), and chemotherapy-free regimens incorporating oral targeted therapies such as ibrutinib (Ibr), acalabrutinib (Acala), or venetoclax (Ven). Most chemotherapy-free regimens require continuous treatment to progression, while Ven plus G (VenG) is given for a fixed duration of 12 months, based on the CLL14 trial that led to its approval. Fixed-duration VenG has the potential for cost savings compared with treat-to-progression chemotherapy-free regimens. OBJECTIVE: To evaluate the cost-effectiveness of 12 months fixed-duration VenG in first-line treatment of unfit patients with CLL from a US health care payer perspective compared with GClb, BR, Ibr, Ibr + G, Ibr + R, Acala, and Acala + G. METHODS: A partitioned survival model was developed with 3 health states: progression-free survival (PFS), postprogression survival, and dead. The patient population, as based on the CLL14 trial, comprised previously untreated unfit patients with CLL (mean age 71.1 years, 33.1% female). The distribution of patients in each health state over time was estimated using extrapolated PFS and overall survival (OS) curves for VenG and GClb, based on CLL14 data 2 or more years after treatment cessation. PFS and OS for the other comparators were estimated using hazard ratios vs VenG, based on a network metaanalysis. Adverse events, utility values, and costs were obtained from published literature. The model estimated life-years gained, quality-adjusted life-years (QALYs) gained, and costs. The time horizon was 20 years, with a cycle time of 28 days. Outcomes and costs were discounted at 3.0% per year, and costs were estimated from a US health care payer perspective. One-way and probabilistic sensitivity analyses were conducted. RESULTS: In this cross-trial analysis of unfit CLL patients, in the base case, VenG had lower projected total costs than all comparators investigated. VenG also had larger projected health benefits (more QALYs gained) than GClb, BR, Ibr, and Ibr + R. VenG was therefore more effective and less costly than these comparators (dominant). Ibr + G, Acala, and Acala + G showed higher QALYs gained vs VenG (0.022, 0.672, and 0.961, respectively), and substantially higher projected costs vs VenG ($1,488,400, $1,579,737, and $1,656,154, respectively). Thus, Ibr + G, Acala, and Acala + G would cost more than $1,000,000 per QALY gained vs VenG. At the commonly used willingness-to-pay threshold of $150,000 per QALY gained, Ibr + G, Acala, and Acala + G were not cost-effective compared with VenG. CONCLUSIONS: Fixed-duration VenG for 12 months is a cost-effective first-line treatment option for unfit CLL patients compared with other available options and provides value for money to US health care payers at a threshold of $150,000 per QALY gained. Future studies with longer trial follow-up and more mature survival data may help to confirm longer-term cost benefits of VenG. DISCLOSURES: Genentech Inc. and AbbVie provided financial support for this study. Genentech Inc., AbbVie, and Pharmerit - An OPEN Health Company participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Venetoclax is being developed in a collaboration between Genentech Inc. and AbbVie. Ravelo and Shapouri are employed by Genentech Inc. and have ownership interests. Manzoor and Sail are employed by AbbVie and have ownership interests. Chatterjee, van de Wetering, and Qendri, employees of Pharmerit - An OPEN Health Company, received consultancy fees from AbbVie. Davids has received consultancy fees from AbbVie, AstraZeneca, Eli Lilly, Genentech Inc., Janssen, MEI Pharma, Novartis, Pharmacyclics, and Verastem; research funding from Ascentage Pharma, Genentech Inc., MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, and Verastem; and has served on board of directors or advisory committees for AbbVie, Adaptive Biotechnologies, AstraZeneca, BeiGene, Eli Lilly, Genentech Inc., Janssen, Pharmacyclics, TG Therapeutics, and Verastem. This study was presented as a poster at ASH 61st Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

BACKGROUND: Treatment of chronic lymphocytic leukemia (CLL) with a fixed-duration venetoclax (Ven)-based regimen is now a standard of care (SOC) option for both frontline and relapsed refractory (R/R) disease based on results of the CLL14 and MURANO trials (Fischer et al NEJM 2019, Seymour et al NEJM 2018). As fixed-duration Ven regimens are now a SOC, it is expected that an increasing number of patients (pts) will ultimately progress after Ven exposure and require additional CLL-directed therapy. While many discuss re-treatment with Ven as a subsequent treatment option, the current literature contains response data on an extremely limited number of evaluable pts (11 pts MURANO, overall response rate (ORR) 55%; 3 pts VEN 365, ORR 100%). Whether re-treatment with Ven is an acceptable option remains an important unanswered clinical question. METHODS: We conducted a multicenter, retrospective study of CLL pts treated with a Ven-based regimen (Ven1) and then re-treated with a second Ven-based regimen (Ven2) in a later line of therapy (LOT). Data were collected from 13 centers and the CLL Collaborative Study of Real-World Evidence database. CLL pts were eligible for inclusion if they were treated with a Ven-based regimen in any LOT and then re-treated with a Ven-based regimen as a later LOT. Collected data included demographics, prognostic disease characteristics, tumor lysis syndrome (TLS) risk and incidence, clinical response and reasons for treatment discontinuation (dc). The primary study endpoint was investigator-assessed ORR (CR: complete response, PR: partial response, SD: stable disease, PD: progression of disease, iwCLL 2018). Kaplan-Meier method was used to estimate progression free survival (PFS). All other analyses were descriptive. RESULTS: We identified 25 pts who were re-treated with Ven. Pt characteristics prior to treatment with Ven1 are summarized in Table 1. In 24% of pts (n=6), Ven1 was administered as part of a clinical trial. Median prior LOT was 2 (range 0-10) with 12.0% treatment naïve and 60% with prior BTKi exposure. The majority of pts had ≥1 high-risk prognostic marker: del17p (39%), TP53 mut (27%), complex karyotype ≥5 abnormalities (30%) and unmutated IGHV (84%). For Ven1, treatment regimens, TLS risk, and dose are summarized in Table 2. With a median duration of exposure of 15 months (mos) (64% pts > 12 mos) for Ven1, the ORR was 88% (CR: 48%, PR: 40%, Figure 1A). Ten pts had minimal residual disease (MRD) assessments by flow cytometry; 8 pts (80%) achieved undetectable MRD (10^-4). Most common reasons for Ven1 dc included: toxicity (28%), completion of planned therapy (24%), MD/pt preference (24%), other (12%), alloHSCT (4%) and cost (4%). There was a median of 8.7 mos (36% > 12 mos) between Ven1 and the initiation of Ven2, and 88% did not receive another LOT between Ven1 and Ven2. Reasons for Ven2 initiation were either CLL progression (87.5%) or MRD-positive relapse (12.5%). For Ven2, TLS risk, TLS incidence and dose information are outlined in Table 2. TLS was a rare event during Ven re-treatment (4.5%, lab only). For Ven2, Ven monotherapy was the most common regimen (52%). Standard Ven dose-escalation was used for re-initiation in 17 of 19 pts with available data, however 1 pt started Ven2 at 400 mg daily (no TLS) and another underwent a prolonged ramp-up period. At the time of this analysis, 18 pts had available response assessments for Ven2: ORR is 72.2% (CR: 4, PR: 9, SD: 4 and PD: 1, Figure 1B). Median time from Ven2 to progression or last follow up is 8 mos (0.2-29 mos). Median PFS has not been reached. Estimated 12-month PFS is 69.1%. For pts with a CR to Ven2, median follow up time is 14.5 mos vs 7 mos for pts with PR or SD. Of 25 pts re-treated with Ven, 68% remain on Ven2 presently and 32% have discontinued Ven2, including due to CLL progression (n=4), completion of planned therapy (n=1), unrelated death (n=1), MD/pt preference (n=1). CONCLUSIONS: To our knowledge, this is the largest reported cohort of CLL pts re-treated with Ven after a prior Ven-based regimen. The high ORR in this pt population (median 2 prior therapies) suggests that re-treatment is a promising strategy and should be considered in treatment sequencing algorithms. Notably, pts with a CR to Ven2 had a longer median follow up than those with a PR or SD, suggesting a likelihood of deeper responses with time. Given the promising ORR, further research to prospectively validate Ven re-treatment is warranted. Updated data will be presented. Disclosures Allan: Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria; Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:Abbvie: Current Employment, Other: may hold stock or stock options. Pu:Takeda Pharmaceuticals: Consultancy. Barr:Gilead: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Morphosys: Consultancy; TG therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy. Coombs:LOXO Oncology: Honoraria; MEI Pharma: Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria; Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding. Skarbnik:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy; Beigene: Speakers Bureau; Verastem: Speakers Bureau; Novartis: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CLL Society: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rhodes:Verastem: Consultancy; Abbvie/Genentech: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy. Barrientos:Janssen: Honoraria; Sandoz: Consultancy; Oncternal Therapeutics: Research Funding; Bayer: Consultancy; Genentech: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy. Roeker:American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Leslie:Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kamdar:Roche: Research Funding. Choi:Pharmacyclics/Abbvie: Research Funding; Genentech: Consultancy. Simkovic:Abbvie: Consultancy, Other: travel expenses. Lansigan:Seattle Genetics: Consultancy; BMS: Consultancy; BMS Steering Committee for MAGNIFY Program: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharma: Consultancy, Research Funding. Zelenetz:Novartis: Consultancy; Gilead: Research Funding; Janssen: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech/Roche: Consultancy; Roche: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnology: Consultancy; MorphoSys: Research Funding; Amgen: Consultancy; Sandoz: Research Funding; Celgene: Research Funding; MEI Pharma: Research Funding. Moskowitz:Merck: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Miragen Therapeutics: Consultancy; Incyte: Research Funding; Merck: Consultancy; Imbrium Therapeutics, L.P.: Consultancy; Seattle Genetics: Consultancy. Goy:Morphosys: Research Funding; AbbVie: Research Funding; MD Anderson: Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Infinity Verastem: Research Funding; Infinity: Research Funding; Karyopharm: Research Funding; Genentech/Roche: Research Funding; CALBG: Research Funding; Constellation: Research Funding; Bayer: Research Funding; PracticeUpdate Oncology: Consultancy; RCCA/OMI: Current Employment; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; Xcenda: Consultancy; Hackensack UMC and University of Nebraska: Research Funding. Feldman:Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Trillium: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Furman:Verastem: Consultancy; Genentech: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy, Research Funding; Sunesis: Consultancy; Pharmacyclics: Consultancy; Oncotarget: Consultancy; Loxo Oncology: Consultancy; Janssen: Consultancy, Speakers Bureau; Incyte: Consultancy. Mato:Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Adaptive: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding.

OBJECTIVES To examine the knowledge, attitudes, and interest of an inner-city population toward pharmacogenetic testing, with the primary objective of identifying facilitators and barriers toward pharmacogenetic testing; and secondary objectives of determining predictors of patient interest in pharmacogenetic testing and how much patients would pay for the test. METHODS Patients were recruited from an Antithrombosis Clinic from March to April 2014. A cross-sectional 19-question survey was administered in person to determine patients' knowledge and awareness of pharmacogenetic testing and collect demographic information. After explaining pharmacogenetics, patients ranked their interest toward the test and answered open-ended questions that elicited facilitators and barriers toward pharmacogenetic testing and elucidated how much patients would pay for testing. RESULTS A total of 120 patients (mean age 55.0 ± 14.0 years, 39.2% male, 69.2% African American) were surveyed. Facilitators included providing further information about pharmacogenetic testing; elaborating on benefits of testing to predict treatment efficacy; patients' trust in their providers to make correct genotype-guided prescribing decisions; and insurance coverage and test affordability. Barriers to testing included concerns about the negative consequences associated with test results; burden of the testing process; perceived lack of utility among elderly and those whose medications were working; privacy issues; and concerns regarding insurance coverage and test affordability. Women had 4.2 times higher adjusted odds of being interested in pharmacogenetic testing. Almost half (44.4%) of the patients with high interest in the test were willing to pay $20 or more, whereas 76.2% of patients with low interest wanted testing at no cost. CONCLUSION This study identified facilitators, such as providing additional pharmacogenetic test information, and barriers, such as perceived negative impact of the results and test utility, as issues to address when engaging an urban, largely minority population in pharmacogenetic testing. Female sex was a predictor of interest toward pharmacogenetic testing. These facilitators and barriers should be taken into consideration as pharmacogenetic testing gains widespread utility among inner-city populations.

Real-world evidence focusing on medication switching patterns amongst direct oral anticoagulant (DOACs) has not been well studied. The objective of this study is to evaluate patterns of prescription switching in non-valvular atrial fibrillation (NVAF) patients initiated on a DOAC and previously naive to anticoagulation (AC) therapy. Data was obtained from Truven Health MarketScan® Commercial and Medicare Supplemental database (2009-2013). AC naive (those without prior anticoagulant use) NVAF patients initiated on a DOAC, with 6 months of continuous health plan enrollment before and after treatment initiation and maintained on continuous therapy for a minimum of 6 months were included. Of 34,022 AC naive NVAF patients initiating a DOAC, 6613 (19.4%) patients switched from an index DOAC prescription to an alternate anticoagulant and 27,409 (80.6%) remained on the DOAC [age: 68.5 ± 11.7 vs. 67.1 ± 12.7 years, p

Objective: To perform a systematic review to evaluate the quality of warfarin anticoagulation control in outpatient pharmacist-managed anticoagulation services (PMAS) compared with routine medical care (RMC). Data Sources: MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, and Cochrane CENTRAL, from inception to May 2017. Search terms employed: (“pharmacist-managed” OR “pharmacist-provided” OR “pharmacist-led” OR “pharmacist-directed”) AND (“anticoagulation services” OR “anticoagulation clinic” OR “anticoagulation management” OR “anticoagulant care”) AND (“quality of care” OR “outcomes” OR “bleeding” OR “thromboembolism” OR “mortality” OR “hospitalization” OR “length of stay” OR “emergency department visit” OR “cost” OR “patient satisfaction”). Study Selection and Data Extraction: Criteria used to identify selected articles: English language; original studies (comments, letters, reviews, systematic reviews, meta-analyses, editorials were excluded); warfarin use; outpatient setting; comparison group present; time in therapeutic range (TTR) included as a measure of quality of anticoagulant control; study design was not a case report. Data Synthesis: Of 177 articles identified, 25 met inclusion criteria. Quality of anticoagulation control was better in the PMAS group compared with RMC in majority of the studies (N = 23 of 25, 92.0%). Clinical outcomes were also favorable in the PMAS group as evidenced by lower or equal risk of major bleeding (N = 10 of 12, 83.3%) or thromboembolic events (N = 9 of 10, 90.0%), and lower rates of hospitalization or emergency department visits (N = 9 of 9, 100%). When reported, PMAS have also resulted in cost-savings in all (N=6 of 6, 100%) of studies. Conclusions: Compared with routine care, pharmacist-managed outpatient-based anticoagulation services attained better quality of anticoagulation control, lower bleeding and thromboembolic events, and resulted in lower health care utilization.

OBJECTIVES: To estimate the cost-effectiveness of venetoclax + obinutuzumab (GAZYVA®, G), (VEN+G) in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL) from a Canadian health care system cost perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival (PFS) and overall survival (OS) over a 10-year time horizon. Cost-effectiveness was estimated comparing 12-month fixed duration of VEN+G versus (vs) G + Chlorambucil (GClb) based on the CLL14 clinical trial (NCT02242942). Other comparators included Bendamustine + rituximab (BR), Chlorambucil + rituximab (Clb+R), Ibrutinib (Ibr), Acalabrutinib (Acala) and Acalabrutinib + GAZYVA (Acala+G). VEN+G was also compared to the combination of fludarabine, cyclophosphamide and rituximab (FCR) in the overall 1L CLL population which included unfit and fit patients. Relative efficacy of VEN+G vs other comparators was estimated using a network meta-analysis. Health state utilities and adverse event disutilities were derived from a systematic literature review and other published sources. Costs included CLL treatment, routine care and monitoring, adverse events, disease progression costs, subsequent treatment costs, and end of life care. Uncertainty was assessed using an underlying probabilistic model (probabilistic analysis of uncertainty generated from 5,000 iterations), through deterministic sensitivity analyses (i.e., one-way sensitivity analyses (OWSA)), and through a series of alternative scenario analyses. RESULTS: For the overall unfit 1L CLL patient population, the probabilistic total discounted costs incurred over a 10-year time horizon were as follows: $217,727 for VEN+G vs $312,287 for GClb, $399,219 for BR, $380,713 for Clb+R, $736,017 for Ibr, $868,797 for Acala and $916,139 for Acala+G. The probabilistic total discounted quality adjusted life years (QALYs) were 4.964 for VEN+G vs 4.750, 4.550, 4.422, 4.709, 5.269, and 5.359, respectively for the comparators. For the overall 1L CLL patient population, the probabilistic total discounted costs were $219,651 for VEN+G vs $312,570 for GClb, $342,195 for FCR, $397,262 for BR, $380,551 for Clb+R, $757,129 for Ibr, $868,388 for Acala, and $916,798 for Acala+G. The probabilistic total discounted QALYs were 5.888 for VEN+G vs 5.519, 5.067, 5.198, 5.073, 5.597, 6.259 and 6.380, respectively for the comparators. VEN+G was found to be less costly and more efficacious (i.e., dominant) compared to GClb, BR, Clb+R, Ibr and FCR. As a result, incremental cost utility ratios (ICERs) were not calculated for these comparators. Acala and Acala+G resulted in ICERs ranging from $1.4-$2.1 million per QALY gained relative to VEN+G, which is not cost-effective. Based on the probabilistic model and 5,000 simulations, VEN+G was found to be at least 97% cost-effective across all decision maker willingness-to-pay thresholds. The results from the deterministic model were found to be similar to the probabilistic model. Using the deterministic model, and in comparison to the most commonly prescribed treatment for 1L CLL in Canada (i.e., Ibr), the OWSA comparing VEN+G to Ibr found that the most influential variables in the model were the PFS and OS hazard ratios for Ibr and the utility values for PFS and post-progression survival. CONCLUSION: VEN+G is an effective novel fixed duration treatment option which leads to deep and durable responses for the treatment of patients with unfit 1L CLL and provides excellent value-for-money compared with existing chemoimmunotherapy and treat to progression novel combinations. Disclosures Chatterjee: Pharmerit: Current Employment. Van de Wetering:Pharmerit: Current Employment. Goeree:AbbVie Inc.: Consultancy. Desbois:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzi:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:AbbVie: Current equity holder in publicly-traded company. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company.

Background Evidence of adherence and persistence patterns in anticoagulation (AC) therapy comparing treatment-naive and non-naive patients is lacking. The objective of this study was to evaluate patterns of medication adherence and persistence in a real-world setting among AC-naive and AC-experienced atrial fibrillation (AF) patients treated with direct oral anticoagulants (DOACs). Methods AF patients newly initiating a DOAC with a minimum of 6 months of continuous health plan enrollment pre and post-index date (first DOAC prescription) were identified from the Truven Health MarketScan® Commercial and Medicare Supplemental databases (2009-2013). DOAC adherence (proportion of days covered [PDC]), persistence, and predictors of adherence were assessed at 6 and 12 months post-index. Results Of 66,090 AF patients included, 46.6% (n=30,826) were AC-naive and 53.4% (n=35,264) were AC-experienced (age: 66.9±12.7 vs. 70.4±11.4 years, p

INTRODUCTION: Historically chemoimmunotherapy has been the standard of care in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL). More recently several effective oral targeted agents, such as ibrutinib-based regimens, have provided effective chemotherapy-free treatment options in CLL. However, these therapies require continuous treatment until disease progression. Recently FDA approved (May 2019), venetoclax plus obinutuzumab (VenG) is a highly effective chemotherapy-free therapy that is used over a 12-month fixed treatment duration (Fischer et al, N Eng J Med 2019). The objective of this study is to estimate the cost-effectiveness of VenG in the treatment of 1L CLL from a US-payer perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival and overall survival over a lifetime horizon (20 years). Cost-effectiveness was estimated by comparing a 12-month fixed duration of VenG versus (vs.) chlorambucil-obinutuzumab (ClbG) based on the CLL14 clinical trial (NCT02242942). Other comparators included treat-to-progression therapies, such as ibrutinib (IBR), IBR + rituximab (IR), and IBR + G (IG), and a 6-month course of bendamustine + rituximab (BR). Using a network meta-analysis, the relative efficacy of VenG and ClbG vs. other selected comparators was estimated. Health state utilities and adverse event (AE) disutilities were derived from a systematic literature review and published health-technology assessment reports. To generate total quality-adjusted life years (QALYs), these health state utilities and AE disutilities were applied to the relative efficacy data. US-specific costs included those for CLL treatment, routine care and monitoring, AEs, disease progression (including subsequent treatment), and end-of-life care. Cost-effectiveness results are presented in terms of incremental cost per QALY. A new treatment that is both lower in total cost and more efficacious (in QALYs) vs. identified comparator treatments is described as being "dominant". Uncertainty in the model was tested through deterministic, probabilistic, and scenario analyses. RESULTS: The benefits in the cost-effectiveness model (CEM) were measured in terms of total discounted QALYs which were 6.47 for VenG, 6.12 for ClbG, 6.11 for IBR, 6.08 for IR, 6.41 for IG, and 5.98 for BR. The total discounted costs incurred by VenG and ClbG were $322,613 and $847,571, respectively. IBR-based treat-to-progression regimens incurred total discounted costs of $1,485,368 for IBR, $1,447,010 for IR, and $1,988,706 for IG. BR incurred total discounted costs of $808,756. Compared to these regimens, VenG is less costly (incremental cost ranges between: -$1,666,093 to -$486,143). The incremental discounted QALYs of VenG was: 0.36 vs. GC, 0.49 vs. BR, 0.37 vs. IBR, 0.06 vs. IG, and 0.39 vs. IR. Thus, VenG with a 12-month fixed duration, has lower total costs and is more efficacious ("dominant") over all comparators in the CEM. The probabilistic sensitivity analysis results were in line with the deterministic results. Sensitivity analysis indicated the post-progression survival utility was the most influential parameter on the model outcomes. As the CLL14 trial data matures, these cost-effectiveness estimates may change and additional scenarios for post-progression survival for VenG will be explored. Updated results will be presented. CONCLUSIONS: VenG is projected to be cost-effective vs. ClbG within accepted US cost-effectiveness thresholds. Compared with BR and IBR-based treat-to-progression regimens (IBR, IR, and IG), a 12-month fixed-duration treatment option with VenG seems cost saving and more efficacious based on the CEM. Taken together, VenG appears to be a cost-effective standard therapy for 1L CLL patients. Disclosures Davids: AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding. Ravelo:Genentech: Employment, Equity Ownership. Shapouri:Roche: Equity Ownership; Genentech, Inc.: Employment. Manzoor:AbbVie: Employment, Other: and may hold stock or stock options. Sail:AbbVie: Employment, Other: and may hold stock or stock options. Van de Wetering:AbbVie: Consultancy. Hallek:Roche, Gilead Sciences, Inc., Mundipharma, Janssen, Celgene, Pharmacyclics, AbbVie: Honoraria, Research Funding, Speakers Bureau.

BACKGROUND Novel agents have changed the treatment landscape in chronic lymphocytic leukemia (CLL), however little has been reported about real-world treatment sequence patterns and associated outcomes post-introduction of novel agents. Studies have demonstrated that venetoclax is effective for patients (pts) who have discontinued ibrutinib, however treatments and outcomes post-venetoclax discontinuation remain unclear. The objective of this study was to examine real-world treatment sequence patterns post-introduction of novel agents and specifically understand treatment sequencing following venetoclax. METHODS The CLL Collaborative Study of Real-World Evidence (CORE) is a retrospective, multicenter, collaborative observational study of pts with CLL/small lymphocytic leukemia (SLL). For this analysis, adult pts were eligible for inclusion if they started therapy for CLL/SLL in the relapsed/refractory setting after February 12, 2014 (FDA approval date of first novel agent for CLL/SLL). Interim data are presented; data collection for this analysis is ongoing and is expected to be completed by October 31, 2019. Treatment sequences were characterized specifically focusing on treatment sequencing following venetoclax and other novel agents (i.e., BCRi: e.g., ibrutinib, idelalisib or acalabrutinib). Clinical response, as assessed by physician, was also reported from medical charts (iwCLL criteria were provided as a reference only). RESULTS Of the 267 pts available at the time of interim data analysis, 231 pts (87%) received a novel agent in at least one line of therapy (first-line: 35 pts [15%]; second-line: 133 pts [58%]; third-line or later: 63 pts [27%]). Among novel agents, ibrutinib was the most commonly used first novel agent for 198 pts (86%) followed by venetoclax for 18 pts (8%) and idelalisib for 12 pts (5%). Of those 267 pts, 143 pts (54%) received chemotherapy/chemoimmunotherapy (CT/CIT) followed by a novel agent; 63 pts (24%) received a novel agent followed by a novel agent; 17 (7%) received a novel agent followed by CT/CIT; and 47 (18%) received a CT/CIT followed by CT/CIT. At the time of this interim data cut there were 220 pts (82%) who received BCRi-based regimens (first-line: 33 pts [15%]; second-line: 123 pts [56%]; third-line or later: 64 pts [29%]) and 62 pts (23%) who received venetoclax-based regimens (first-line: 2 pts [3%]; second-line: 22 pts [36%]; third-line or later: 38 pts [61%]). Of the 220 pts who received BCRi-based regimens, 50 (23%) achieved complete remission (CR) and 83 (38%) achieved partial remission (PR) (responses based on physician assessment). Of the 220 pts, 88 (40%) went on to receive a subsequent line of therapy. The most common subsequent treatments administered were venetoclax containing regimens (n= 34, 39%). Of the 88 pts who received a subsequent line of therapy after BCRi-based regimens, 22 pts (25%) achieved CR and 24 pts (27%) achieved PR. Of the 62 pts who received venetoclax-based regimens, 20 pts (32%) achieved CR and 14 pts (23%) achieved PR. Of the 62 pts, 15 pts (24%) went on to receive a subsequent line of therapy. The most common subsequent treatment administered were BCRi containing regimens (n= 10, 67%) primarily ibrutinib-based. Of the 15 pts receiving a subsequent line of therapy after venetoclax-based regimens, 3 pts (20%) achieved CR and 4 pts (27%) achieved PR. While preliminary results are encouraging, further data collection efforts are ongoing and will be included for presentation to confirm the results and outcomes associated with different sequencing options. CONCLUSIONS The treatment paradigm is evolving with the introduction of novel agents. Results from this study will provide a baseline description of treatment sequence patterns enabling clinicians to benchmark the impact of the introduction of novel agents and associated outcomes. Early evidence from these results also suggests that novel agents are most commonly introduced during second line treatment and that other novel agents, including ibrutinib, following venetoclax treatment are being utilized in the real-world settings. Table. Disclosures Mato: Pharmacyclics: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; DTRM Biopharma: Research Funding; Johnson & Johnson: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; Acerta: Consultancy; Janssen: Consultancy; Gilead: Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Celgene: Consultancy. Sail:AbbVie: Employment, Other: may hold stock or stock options. Yazdy:Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy; Bayer: Honoraria, Speakers Bureau. Hill:Amgen: Research Funding; Seattle Genetics: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Shadman:Bigene: Research Funding; TG Therapeutics: Research Funding; AbbVIe: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy; Sound Biologics: Consultancy; Pharmacyclics: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Atara: Consultancy; Verastem: Consultancy; Mustang Biopharma: Research Funding; Gilead: Research Funding; Merck: Research Funding; Acerta: Research Funding; Emergent: Research Funding; Celgene: Research Funding; Sunesis: Research Funding. Manzoor:AbbVie: Employment, Other: and may hold stock or stock options. Tuncer:Abbvie: Membership on an entity's Board of Directors or advisory committees; 2018 Steering Committee: Other: reimbursement for travel to the steering committee at ASH. Allan:Janssen: Consultancy, Honoraria; Acerta Pharma: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie company: Consultancy; Verastem Oncology, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Sunesis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ujjani:PCYC: Research Funding; Pharmacyclics: Honoraria; AbbVie: Honoraria, Research Funding; Genentech: Honoraria; Atara: Consultancy; Astrazeneca: Consultancy; Gilead: Consultancy. Sharmokh:AbbVie: Employment, Other: may hold stock or stock options. Jiang:AbbVie: Employment, Other: and may hold stock or stock options. Pena:AbbVie: Employment, Other: and may hold stock or stock options. Marshall:AbbVie: Employment, Other: and may hold stock or stock options. Nielsen:AbbVie: Employment, Other: and may hold stock or stock options. Barr:Janssen: Consultancy; Astra Zeneca: Consultancy, Research Funding; Verastem: Consultancy; Genentech: Consultancy; Seattle Genetics: Consultancy; Merck: Consultancy; Celgene: Consultancy; TG Therapeutics: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding; AbbVie: Consultancy; Gilead: Consultancy. Brown:Pfizer: Consultancy; Pharmacyclics: Consultancy; Sunesis: Consultancy; Teva: Honoraria; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Sun: Research Funding; Sun Pharmaceuticals, Inc: Research Funding; Morphosys: Other: Data safety monitoring boards ; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Catapult Therapeutics: Consultancy; Dynamo Therapeutics: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Invectys: Other: other; Janssen: Honoraria; Kite: Consultancy, Research Funding; Loxo: Consultancy, Research Funding; Novartis: Consultancy; Octapharma: Consultancy. Schuh:Pharmacyclics: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Janssen: Speakers Bureau; Verastem: Speakers Bureau; Kite: Speakers Bureau; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; Bristol-Myers Squibb: Research Funding. Eyre:Janssen: Honoraria, Other: travel support; Gilead: Honoraria, Other: travel support; AbbVie: Honoraria, Other: travel support. Wierda:Pharmacyclics LLC: Research Funding; Juno Therapeutics: Research Funding; Gilead Sciences: Research Funding; Miragen: Research Funding; Cyclcel: Research Funding; Oncternal Therapeutics Inc.: Research Funding; GSK/Novartis: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Acerta Pharma Inc: Research Funding; KITE pharma: Research Funding; Sunesis: Research Funding; Loxo Oncology Inc.: Research Funding; Janssen: Research Funding; AbbVie: Research Funding. Skarbnik:Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Verastem Oncology: Honoraria, Research Funding, Speakers Bureau; Kite Pharma: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Acerta: Research Funding; Genentech: Honoraria, Speakers Bureau; CLL Society: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Speakers Bureau; Novartis: Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Roeker:Abbott Laboratories: Equity Ownership; AbbVie: Equity Ownership. Bannerji:Gilead: Other: travel support; Celgene: Consultancy; Celgene: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Merck: Other: travel support, Patents & Royalties: IP rights; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Pharmacyclics: Other: travel support; AbbVie, Inc: Consultancy; Pharmacyclics: Other: travel support; Gilead: Other: travel support; AbbVie, Inc: Consultancy, travel support; Merck: Other: travel support, Patents & Royalties: IP rights. Pauff:AbbVie Inc: Employment, Other: may own stock or stock options. Schuster:Novartis, Nordic Nanovector, and Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: a patent (with royalties paid to Novartis) on combination therapies of CAR and PD-1 inhibitors.; Novartis, Celgene, Genentech, Merck, Pharmacyclics, Acerta, and Gilead: Other: Grants, Research Funding; Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, Acerta, and Celgene: Honoraria. Follows:Roche: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau. Cheson:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Gilead: Research Funding; Epizyme: Research Funding. Eichhorst:Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BeiGene: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ArQule: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Brander:Genentech: Consultancy, Honoraria, Research Funding; DTRM Biopharma: Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Research Funding; BeiGene: Research Funding; Novartis: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; Acerta: Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; MEI: Research Funding. Pivneva:AbbVie: Other: employee of Analysis Group, Inc., which has received consultancy fees from AbbVie. Lamanna:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding; AbbVie: 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; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding.

BACKGROUND The recent approval of novel agents (NAs) has changed the treatment landscape in chronic lymphocytic leukemia (CLL), however, there remains uncertainty regarding treatment discontinuation patterns in real-world (RW) settings. This study assessed patterns of and reasons for discontinuation for patients (pts) treated with chemotherapy/chemoimmunotherapy (CT/CIT) and NAs in first (1L) and second (2L) lines of therapy in CLL. METHODS The CLL Collaborative Study of Real-World Evidence (CORE) study is a retrospective, multicenter, observational study. Adult CLL patients (pts) were included if they were diagnosed with CLL, initiated 1L or 2L therapy for CLL on/after 01/01/2012 (excluding lines of therapy received as part of clinical trials). Discontinuation patterns were assessed among CT/CIT and NAs, more specifically in four treatment cohorts: fludarabine+cyclophosphamide+rituximab (FCR), bendamustine+rituximab (BR), B-cell receptor inhibitors (BCRi)-based (e.g., acalabrutinib, ibrutinib, or idelalisib) and venetoclax-based regimens. Treatment discontinuation was operationally defined as ending therapy for reason(s) other than completion of planned duration of therapy. RESULTS Of 671 pts receiving 1L therapy, 81 (12%) received FCR (median age=58, 70% males); 153 (23%) BR (median age=63, 61% males), 255 (38%) BCRi-based (median age=65, 65% males); and 13 (2%) venetoclax-based (median age=59, 54% males). The remaining 169 pts received other regimens (e.g., other CT/CIT). The most common BCRi-based therapy in 1L was ibrutinib-containing regimens (97%). Median duration of follow-up was 24, 27, 11 and 8 months for FCR, BR, BCRi-based and venetoclax-based regimens, respectively. Treatment discontinuation occurred in 18 (22%), 41 (27%), 51 (20%) and 4/13 pts receiving FCR, BR, BCRi-based and venetoclax-based regimens, respectively. The most common reason for discontinuation in FCR (11/18 pts; 61%), BR (15/41 pts; 37%) and BCRi-based (24/51 pts; 47%) cohorts was adverse events (AEs), with >70% being severe AEs in each cohort. Common AEs leading to discontinuations were hematological abnormalities (e.g., neutropenia, thrombocytopenia) in the FCR (6/18 pts; 33%) and BR (6/41 pts; 15%) cohorts. In the BCRi-based cohort the most common AEs leading to discontinuations were cardiac (4/51 pts; 8%), skin and subcutaneous tissue disorders (e.g., rash; 6/51 pts; 12%), hemorrhage/bleeding (3/51; 6%), and musculoskeletal and connective tissue disorders (3/51; pts; 6%). For the relatively small number of pts treated with venetoclax-based regimens and discontinued, disease progression was the common reason for discontinuations (3/4 pts); no pts discontinued venetoclax-based regimens due to adverse events. In the relapsed/refractory setting specifically in 2L, 15 (7%), 113 (56%) and 16 (8%) pts received BR, BCRi-based and venetoclax-based regimen respectively, of which the most common BCRi-based therapy regimen was ibrutinib-based (95%). Treatment discontinuation occurred in 5/15 pts (33%), 27/113 pts (24%) and 4/16 pts (25%) receiving BR, BCRi-based and venetoclax-based regimens, respectively. The most common reason for discontinuations were severe AEs for BR (3/5 pts) and BCRi-based (13/27 pts) cohorts and disease progression for venetoclax-based regimens (2/4). CONCLUSIONS Despite the relatively short follow-up, in both 1L and 2L, similar discontinuation patterns emerge. CT/CIT is often discontinued prior to completion of planned cycles of therapy, suggesting that these regimens are difficult to tolerate. Additionally, treat to progression BCRi-based regimens are also discontinued for severe AEs, discordant to results from clinical trials. With a small cohort and limited information collected, results on venetoclax discontinuation warrants additional studies. Well tolerated chemotherapy-free combinations with finite treatment duration in treatment naïve and relapsed/refractory settings may limit continuous exposure to treatment and prevent discontinuations due to AEs. Table Disclosures Shadman: Atara: Consultancy; Gilead: Research Funding; TG Therapeutics: Research Funding; Bigene: Research Funding; Celgene: Research Funding; Acerta: Research Funding; Emergent: Research Funding; Sunesis: Research Funding; Merck: Research Funding; AbbVIe: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy; Sound Biologics: Consultancy; Mustang Biopharma: Research Funding; Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; ADC Therapeutics: Consultancy. Sail:AbbVie: Employment, Other: and may hold stock or stock options. Manzoor:AbbVie: Employment, Other: and may hold stock or stock options. Yazdy:Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy; Bayer: Honoraria, Speakers Bureau. Hill:AstraZeneca: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG therapeutics: Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Honoraria; Genentech: Consultancy, Research Funding; Takeda: Research Funding; Amgen: Research Funding. Tuncer:Abbvie: Membership on an entity's Board of Directors or advisory committees; 2018 Steering Committee: Other: reimbursement for travel to the steering committee at ASH. Allan:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie company: Consultancy; Janssen: Consultancy, Honoraria; Verastem Oncology, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Consultancy; Sunesis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy. Ujjani:Atara: Consultancy; Gilead: Consultancy; Astrazeneca: Consultancy; Genentech: Honoraria; PCYC: Research Funding; Pharmacyclics: Honoraria; AbbVie: Honoraria, Research Funding. Emechebe:AbbVie: Employment, Other: and may hold stock or stock options. Kamalakar:AbbVie: Employment, Other: and may hold stock or stock options. Sharmokh:AbbVie: Employment, Other: may hold stock or stock options. Jiang:AbbVie: Employment, Other: and may hold stock or stock options. Pena:AbbVie: Employment, Other: and may hold stock or stock options. Marshall:AbbVie: Employment, Other: and may hold stock or stock options. Nielsen:AbbVie: Employment, Other: and may hold stock or stock options. Barr:Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Merck: Consultancy; Seattle Genetics: Consultancy; Genentech: Consultancy; Verastem: Consultancy; Gilead: Consultancy; Astra Zeneca: Consultancy, Research Funding. Brown:Dynamo Therapeutics: Consultancy; Catapult Therapeutics: Consultancy; Invectys: Other: other; Janssen: Honoraria; Kite: Consultancy, Research Funding; Loxo: Consultancy, Research Funding; Novartis: Consultancy; Octapharma: Consultancy; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Teva: Honoraria; Sunesis: Consultancy; Pfizer: Consultancy; Pharmacyclics: Consultancy; Gilead: Consultancy, Research Funding; Genentech/Roche: Consultancy; Sun: Research Funding; Sun Pharmaceuticals, Inc: Research Funding; Morphosys: Other: Data safety monitoring boards ; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy. Schuh:AbbVie: Consultancy, Speakers Bureau; Kite: Speakers Bureau; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; Janssen: Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Verastem: Speakers Bureau; Genentech: Consultancy, Speakers Bureau. Eyre:Janssen: Honoraria, Other: travel support; AbbVie: Honoraria, Other: travel support; Gilead: Honoraria, Other: travel support. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche-Genentech: 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; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Wierda:Gilead Sciences: Research Funding; Juno Therapeutics: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Xencor: Research Funding; Janssen: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; GSK/Novartis: Research Funding; Sunesis: Research Funding; Loxo Oncology Inc.: Research Funding; KITE pharma: Research Funding; Acerta Pharma Inc: Research Funding; Miragen: Research Funding; Pharmacyclics LLC: Research Funding; Cyclcel: Research Funding. Skarbnik:Jazz Pharmaceuticals: Speakers Bureau; Kite Pharma: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; CLL Society: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Acerta: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem Oncology: Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Roeker:Abbott Laboratories: Equity Ownership; AbbVie: Equity Ownership. Bannerji:Celgene: Consultancy; Celgene: Consultancy; Pharmacyclics: Other: travel support; Merck: Other: travel support, Patents & Royalties: IP rights; AbbVie, Inc: Consultancy; Gilead: Other: travel support; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Merck: Other: travel support, Patents & Royalties: IP rights; Pharmacyclics: Other: travel support; AbbVie, Inc: Consultancy, travel support; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Gilead: Other: travel support. Pauff:AbbVie: Employment, Other: and may hold stock or stock options. Schuster:Novartis: Other: a patent (with royalties paid to Novartis) on combination therapies of CAR and PD-1 inhibitors.; Novartis, Celgene, Genentech, Merck, Pharmacyclics, Acerta, and Gilead: Other: Grants, Research Funding; Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, Acerta, and Celgene: Honoraria; Novartis, Nordic Nanovector, and Pfizer: Membership on an entity's Board of Directors or advisory committees. Follows:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Cheson:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Portola: Research Funding; Kite: Research Funding; Gilead: Research Funding; Epizyme: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Eichhorst:BeiGene: Research Funding; ArQule: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Brander:DTRM Biopharma: Research Funding; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Genentech: Consultancy, Honoraria, Research Funding; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Research Funding; Novartis: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; MEI: Research Funding; Tolero: Research Funding; Acerta: Research Funding. Pivneva:AbbVie: Other: employee of Analysis Group, Inc., which has received consultancy fees from AbbVie. Guerin:AbbVie: Other: employee of Analysis Group, Inc., which has received consultancy fees from AbbVie. Mato:AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Celgene: Consultancy; Johnson & Johnson: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Janssen: Consultancy; LOXO: Consultancy, Research Funding; DTRM Biopharma: Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB member, Research Funding.

Objectives To characterize the extent and nature of drug–alcohol interactions in older U.S. adults. Design Cross-sectional. Setting Community. Participants Nationally representative population-based sample of community-dwelling older adults (N = 2,975). Measurements Regular drinkers were defined as respondents who consumed alcohol at least weekly. Medication use was defined as the use of a prescription or nonprescription medication or dietary supplement at least daily or weekly. Micromedex was used to determine drug interactions with alcohol and their corresponding severity. Results One thousand one hundred six (41%) of the participants consumed alcohol regularly, and 567 (20%) were at-risk for a drug–alcohol interaction because they were regular drinkers and concurrently using alcohol-interacting medications. More than 90% of these interactions were of moderate or major severity. Antidepressants and analgesics were the most commonly used alcohol-interacting medications in regular drinkers. Older adult men with multiple chronic conditions had the highest prevalence of potential drug–alcohol interactions. Conclusion The potential for drug–alcohol interactions in the older U.S. adult population may have important clinical implications. Efforts to better understand and prevent the use of alcohol-interacting medications by regular drinkers, particularly heavy drinkers, are warranted in this population.

BACKGROUND Med Guides are the only Food and Drug Administration-regulated source of written patient information distributed with prescriptions drugs. Despite their potential value, studies have found them to have limited utility. OBJECTIVE To evaluate the effectiveness of patient-centered strategies for the design of Med Guides to improve comprehension. DESIGN A cross-sectional, randomized trial. SETTING Two primary care clinics in Chicago, Illinois; one based in a public university hospital and the other within a private academic medical center. PATIENTS A total of 1003 adults aged 18-85 years. INTERVENTION The format and layout of content from 3 typical Med Guides (by reading difficulty, length, exposure) were modified several ways to promote information accessibility. Working with patients, the 3 most preferred versions were evaluated. The first used 2 columns to organize content (Column), a second mimicked over-the-counter "Drug Facts" labeling (Drug Facts), and the third followed health literacy best practices using a simple table format (Health Literacy prototype). MEASURES Tailored comprehension assessment of content from 3 representative Med Guides. RESULTS Comprehension was significantly greater for all 3 prototypes compared with the current standard (all P