ALBERT

Description: Background: Data on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) are mostly available from controlled trials, with limited data from routine clinical practice. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in patients treated for CLL. Methods: Patients with CLL receiving ≥ 1 systemic therapy from 2013-2015 were selected from the Medicare claims database and followed through 2016. The date of the start of first observed therapy served as the index date. Patients were required to have at least 12 months of continuous Medicare enrollment with no evidence of systemic therapy for CLL and/or SCT before the index date. An observed therapy regimen was defined as the combination of all agents received within 35 days after (and including) the first claim for a systemic therapy drug. Therapy was considered ended upon switch to a different regimen or a gap ≥ 90 days after the last treatment. OS was assessed from the index date until the last follow-up or death using the Kaplan-Meier method. Incidence of hematologic and nonhematologic AEs during treatments were assessed for the most commonly observed regimens. The incidence of AEs was based on the presence of at least one claim containing an AE-specific diagnosis code during the treatment, regardless of any history of the AE before treatment initiation. All-cause direct medical costs were assessed from the Medicare's perspective. Results: We analyzed 7965 patients (median age=76 years) who met the inclusion criteria. In the overall study follow-up (across all observed therapy lines), ibrutinib monotherapy (Ibr; n=2708) was the most frequent regimen, followed by chlorambucil monotherapy (Clb; n=1620) and bendamustine/rituximab (BR; n=1485). Median length of follow-up from the index date was 19 months for Ibr, 21 months for Clb, and 24 months for BR. Median OS was reached only for Clb (40.8 months [95% CI = 38.6-not reached]). 24-month OS rates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%), respectively. The incidence of the most frequent AEs (occurrence in 〉10% of patients) are presented in Table1 1; estimates in bold indicate that the incidence of the AE was higher by ≥ 5 percentage points than in the noted trials (Woyach, 2018, N Engl J Med; Burger, 2015, N Engl J Med). The mean per patient per month costs, among all patients, were $1,915 (SD = $2,453) during the baseline period and $8,974 (SD = $11,562) during the period after initiation of the first observed CLL-directed systemic therapy. Mean monthly all-cause costs increased by the number of AEs (from $5,144 [SD = $5,409] among those with 1-2 AEs to $10,077 [SD = $12,542] among those with ≥6 AEs). Conclusion: To our knowledge, this is the largest contemporary observational study reporting outcomes among CLL patients initiating treatments in a real-world setting. Over two-thirds of patients survived ≥2 years after start of the first observed therapy during the study period. Incidence for several hematologic and nonhematologic AEs during the common CLL therapies observed in this study appear to be higher than those reported in the noted clinical trials, highlighting potentially greater susceptibility to these AEs and an unmet medical need in Medicare patients with CLL treated in routine practice. This study also highlights a substantial economic burden that exists in the period after initiation of treatment for CLL. Disclosures Goyal: RTI Health Solutions: Employment. Nagar:RTI Health Solutions: Employment. Kabadi:AstraZeneca: Employment, Equity Ownership. Davis:RTI Health Solutions: Employment. Le:AstraZeneca: Employment, Other: Stocks. Kaye:RTI Health Solutions: Employment.

Description: Background: Most data on overall survival (OS) and adverse events (AEs) in patients with mantle cell lymphoma (MCL) are from controlled trials in academic centers; data from real world management and outcomes in patients with MCL are sparse. We therefore conducted a population-based retrospective cohort study of patients with MCL in the Medicare database to assess treatment patterns, OS, AEs, and economic burden. Methods: Patients with MCL who received any systemic cancer-directed treatment from 2013 to 2015 were selected from the nationwide Medicare claims database and followed through 2016. The date of the first observed systemic therapy defined each patient's index date. Patients were included if they (a) were ≥ 18 years of age at the index date; (b) had ≥ 12 months of continuous Medicare enrollment before the index date (baseline period); and (c) had no evidence of prior MCL-directed treatment (systemic therapy and/or SCT) at any time before the index date (i.e., during at least the previous 12 months). An observed line of therapy was defined as all agents received on or within 35 days after the first claim for a systemic therapy drug; the observed therapy line was considered ended upon switch to another regimen or a gap ≥ 90 days after the last treatment. OS was estimated by the Kaplan-Meier method from the index date (start of first observed line of therapy) until the last follow-up or death. We also calculated rates of occurrence for hematologic and nonhematologic AEs often associated with the most commonly observed regimens (irrespective of observed line of therapy). The occurrence of AEs was defined based on the presence of at least one claim containing an AE-specific diagnosis code during the treatment, regardless of any history of the AE before treatment initiation. All-cause health care costs were assessed from Medicare's perspective. Multivariable models were fitted to assess the association between number of AEs and average costs during the first observed therapy. Results: We analyzed 1,465 patients who met the inclusion criteria (median age=74 years; 68% male; 93% white). Across all observed lines of therapy, ibrutinib monotherapy (Ibr) (n=588 [40%]) was the most frequently used regimen, followed by bendamustine/rituximab (BR) (n=527 [36%]). Ibr recipients had a median age of 75 years, median Charlson Comorbidity Index (CCI) score of 4.0, and were followed for a median duration of 15 months; 52% died during the study period. BR recipients had a median age of 75 years, median CCI score of 3.0, and were followed for a median duration of 21 months; 28% died during the study period. In Ibr recipients, median OS was 22 months (95% CI = 16.9-28.6) and 24-month OS was 47% (95% CI = 42.9%-50.5%). In BR recipients, median OS was not reached while OS at 24 months was 73% (95% CI = 69.4%-76.0%). The occurrence of common AEs during Ibr and BR therapies are presented in Tables 1 and 2. The average per patient per month costs, among all patients, were $2,501 (SD = $2,818) during the baseline period and $12,604 (SD = $14,437) during the period after initiation of the first observed MCL-directed systemic therapy. Multivariable analysis showed that the patients with 3 or more AEs had nearly 4 times higher monthly per patient costs (cost ratio = 4.12, 95% CI = 3.53-4.82) compared with those with 0-2 AEs. Conclusions: Two-year survival rates observed in this study are comparable to those reported in clinical trials (47% for Ibr in the relapsed disease setting [Wang, 2015, Blood]) and nearly 75% for BR in patients with relapsed indolent disease and MCL [Rummel, 2016, Lancet]). Rates of AE occurrence in Ibr- and BR-treated patients in this study highlight the substantial burden and susceptibility to AEs among Medicare patients in the real-world setting. These findings also demonstrate a substantial increase in the economic burden from the baseline period to the period after MCL treatment initiation and as the number of AEs increased. Disclosures Kabadi: AstraZeneca: Employment, Equity Ownership. Goyal:RTI Health Solutions: Employment. Nagar:RTI Health Solutions: Employment. Davis:RTI Health Solutions: Employment. Le:AstraZeneca: Employment, Other: Stocks. Wang:Dava Oncology: Honoraria; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Kite Pharma: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding. Kaye:RTI Health Solutions: Employment.

Description: Introduction: Chronic lymphocytic leukemia (CLL) is an indolent disease most common in elderly adults. While chemo-immunotherapy is a standard first-line (1L) therapy for physically fit patients, treatment options for all CLL patients have greatly increased with the approval of novel agents. Thus, treatment decision-making in CLL has become more challenging, as physicians and patients must consider the risk-benefit trade-offs inherent to treatment options. Yet, little is known about the attitudes, beliefs, and preferences that underlie treatment decision-making in real-world settings for CLL. We aimed to elucidate oncologist/hematologist (ONC) and patient (PT) preferences about key attributes associated with novel CLL treatments using qualitative methods. Methods: In May 2019, we conducted in-depth interviews with 10 ONCs who each manage ≥20 CLL PTs with systemic therapy, prescribe novel agents for CLL, and spend at least 50% of their time in direct PT care. In addition, we interviewed 10 adult PTs with CLL. A commercial healthcare database was used to recruit ONCs, and PTs were recruited via advocacy groups. A trained moderator used a semi-structured interview guide to facilitate interviews focused on attributes influencing CLL treatment decision-making; for ONCs, interviews also asked about factors used to decide whether to treat a PT (vs. active surveillance [AS]). A standardized qualitative coding procedure (content analysis) was used to identify key themes emerging from interview responses. Descriptive statistics are reported to summarize the results. Results: ONCs had a median of 10.5 (range: 7-30) years in practice; most (n=7, 70%) reported working in an academic setting. The decision on whether or not to initiate treatment (vs. AS) depended on multiple factors, primarily symptoms, with patient motivation, health status, and treatment goals playing a lesser role. All ONCs prioritized efficacy when selecting a CLL treatment; progression-free survival (PFS; n=9) and overall survival (OS; n=7) were the top 2 metrics considered. Shorter treatment duration was considered when preferred by the PT or where adherence was a concern. ONCs perceived novel CLL therapies to be effective and well-tolerated; tumor lysis syndrome (TLS; n=8), atrial fibrillation (n=7), and diarrhea (n=7) were among the adverse events (AEs) most often cited as being a concern. ONCs perceived dose reduction as a way to mitigate certain types of AEs. All non-academic ONCs (n=3, 100%) presented one specific treatment to their PTs, but most academic ONCs (n=5, 71%) also discussed options with PTs, even if one specific treatment was recommended. Among PTs, the median age was 62.5 (range: 54-78) years, and most (n=7, 70%) were female. Four (40%) PTs were in 1L, with 4 (40%) in second/later lines (2L+), of treatment for their CLL; 2 (20%) PTs were in AS. Efficacy (described in terms of long-term remission) and concern about the impact of AEs on quality of life (QoL) were of greatest importance to PTs in choosing a treatment. Half reported that their ONC presented a specific recommendation for 1L treatment. Among 1L and 2L+ PTs (n=8), most (n=6, 75%) reported that ONCs did not provide detailed information about AEs associated with their CLL treatment. Across all PTs, cardiac issues and TLS (each, n=7) were the serious AEs most frequently reported as being of concern; other potential AEs, including joint pain (n=5) and brittle fingernails (n=2), were also cited as being of concern. Most PTs (n=9, 90%) expressed their preference for the convenience of oral over intravenous therapy. PTs who had a dose reduction (n=3) reported less apprehension about the potential impact on treatment efficacy than those who never had a dose reduction (n=7). Conclusions: While there was overlap between ONCs and PTs in the most concerning AEs, some PTs cited additional AEs due to the potential impact to their QoL. Regarding treatment preferences, PTs placed high importance on the impact of AEs on QoL, although this was of less importance to ONCs. Unlike ONCs, who viewed dose reductions as a means of resolving certain AEs, some PTs tended to question whether a dose reduction would diminish treatment efficacy. A better understanding of factors that influence treatment preferences may help facilitate ONC-PT communication when selecting novel CLL therapies. Future research should verify if these findings generalize to a representative PT population. Disclosures Le: AstraZeneca: Employment, Other: Stocks. Pendergraft:AstraZeneca: Employment, Equity Ownership. Wahlstrom:AstraZeneca: Employment, Equity Ownership. Ryan:AstraZeneca: Employment, Equity Ownership. Mulvihill:Kantar: Employment. Campbell:Kantar: Employment. Maculaitis:Kantar: Employment. LeBlanc:Helsinn: Consultancy; Jazz Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Duke University: Research Funding; Flatiron: Consultancy; Celgene: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; CareVive: Consultancy; Astra Zeneca: Consultancy, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; NINR/NIH: Research Funding; Pfizer Inc: Consultancy; American Cancer Society: Research Funding; Heron: Membership on an entity's Board of Directors or advisory committees; Medtronic: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction : CLL is the most common chronic leukemia in the US, with nearly 20,000 new cases expected annually. Novel agents, such as ibrutinib, idelalisib, and venetoclax, have been approved in recent years and provide oral options for CLL. However, there is limited data regarding real-world treatment patterns with these novel agents. This study describes dose reduction and discontinuation rates, reasons for both, and outcomes, including overall survival (OS) and duration of therapy (DOT), in CLL patients treated with novel agents. Methods : This is an analysis of a large retrospective cohort study of adult patients (≥ 18 years old) with CLL, treated with novel agents in the VHA from 10/01/2013 to 3/31/2018. Historical data were examined for up to 20 years prior to the enrollment period (10/01/1993 to 9/30/2013). Index date was defined as the date of novel agent initiation. The follow-up period was a minimum of 6 months post index date. Variables, collected via a structured EMR database, included patient demographics, and clinical and treatment characteristics. CLL diagnosis, molecular profiles, and reasons for dose reduction and discontinuation were abstracted by chart review. Descriptive statistics were used to summarize baseline characteristics, treatment patterns, and outcomes. Results: A total of 1205 CLL patients were included in this analysis. Of these, in first observed line, 328 (27%) patients received ibrutinib; in relapsed/refractory observed line (r/r), 741(62%) patients received ibrutinib, 49 (4%) patients on idelalisib, and 87 (7%) patients on venetoclax. Ibrutinib patients in first observed line had a median (range) age of 73 (48-96) years and a median follow-up of 23 (3-54) months after treatment initiation. Dose reduction (n=83, 25%) and discontinuation (n=108, 33%) were frequently due to adverse events (AEs) (93% and 64%). Median DOT to ibrutinib discontinuation was 8 months. The most common AEs leading to dose reduction were major bleed (15%) and rash (15%). The most common AEs leading to discontinuation were atrial fibrillation (20%), major bleed (19%), and infection (11%). The calculated median OS from initiation was 31 (14-49) months. R/R ibrutinib patients had a median age of 72 (45-96) years and had 31 (2-85) months of follow-up after treatment initiation. Dose reduction (n=242, 33%) and discontinuation (n=263, 35%) were frequently due to AEs (89% and 63%). Median DOT to ibrutinib discontinuation was 12 months. The most common AEs leading to dose reduction were thrombocytopenia (13%), arthralgia/myalgia (13%), and infection (12%). The most common AEs leading to discontinuation were atrial fibrillation (19%), infection (15%), and major bleed (11%). the calculated median OS from initiation was 39 (9-57) months. R/R idelalisib patients (n=49) had a median age of 72 (55-93) years and had 27 (3-53) months of follow-up after treatment initiation. Dose reduction (n=8, 16%) and discontinuation (n=41, 84%) were frequently due to AEs (100% and 54%). Median DOT to idelalisib discontinuation was 5 months. The most common AE leading to dose reduction was neutropenia (50%). The most common AEs leading to discontinuation were infection (27%) and pneumonia (18%). R/R venetoclax patients (n=87) had a median age of 72 (47-90) years and had 9 (0-35) months of follow-up after treatment initiation. Dose reduction (n=24, 28%) and discontinuation (n=27, 31%) were frequently due to AEs (100% and 41%). Median DOT to venetoclax discontinuation was 5 months. The most common AEs leading to dose reduction were neutropenia (27%) and thrombocytopenia (27%). The most common AEs leading to discontinuation were neutropenia (36%), thrombocytopenia (18%), and infection (18%). There was not enough follow-up time to have a meaningful OS in this cohort. Conclusions: To our knowledge, this is the largest EMR/chart review study among CLL patients initiating treatments in the real-world setting. This study provides evidence regarding patient characteristics, treatment patterns, and outcomes among patients initiating novel agents for the treatment of CLL in the national VHA population. Dose reduction and discontinuation were frequent across all novel agents, with AEs as the most common reason. These data highlight the significant difference in real world data compared with clinical trial data and indicate the unmet need for more tolerable treatment options for CLL patients. Disclosures Frei: AstraZeneca: Research Funding. Le:AstraZeneca: Employment, Other: Stocks. McHugh:AstraZeneca: Employment. Elesinmogun:AstraZeneca: Employment, Equity Ownership. Obodozie-Ofoegbu:UT Austin: Employment.

Description: Introduction Acalabrutinib was approved by the US Food and Drug Administration on October 31, 2017 for patients with MCL who have progressed on at least one prior therapy and is currently being evaluated in phase III trials for first-line MCL, first-line CLL, and relapsed/refractory (r/r) CLL. Additionally, acalabrutinib received guideline and compendia listing for use in MCL and CLL patients. There is a lack of information on the current treatment patterns with acalabrutinib in real world clinical practice. To that end, we conducted a descriptive analysis of the use of acalabrutinib in the real-world setting for MCL and CLL patients. Methods A retrospective cohort study was conducted using IQVIA's longitudinal prescription (LRx) database linked to the medical claims (Dx) database. Patients ≥18 years old with ≥1 claim for acalabrutinib in LRx between November 1, 2017 and April 30, 2019 were identified; the first claim was index date. Patients were also required to have ≥ 1 Dx claim between November 1, 2016 and April 30, 2019, and ≥ 12 months baseline (defined as ≥ 1 LRx claim and ≥ 1 Dx claim within 12 months pre-index and 〉 12 months pre-index). Patients were required to have ≥2 diagnoses of either MCL or CLL before index (without diagnosis of the other cancer) to create two mutually exclusive cohorts. Patients were excluded if they had data quality issues or evidence of clinical trial enrollment during the study period. Descriptive statistics were used to summarize baseline demographic and clinical characteristics overall and stratified by prior ibrutinib use. Results were described for MCL and CLL cohorts separately. Results A total of 264 MCL and 204 CLL patients treated with acalabrutinib were identified in the study. For both cohorts, the majority (57.2% MCL / 59.3% CLL) were 70 years or older, with a median (interquartile range [IQR]) age of 71.0 (15.0), mean (standard deviation [SD]) of 70.5 (9.7) for MCL and median age of 71.5 (15.0), mean 69.9 (11.1) for CLL patients (Table 1). 76.9% of MCL and 59.8% of CLL patients were male, and over half were commercially insured (50.4% MCL / 52.5% CLL). In the 12-month pre-index period, MCL and CLL patients had a mean (SD) Charlson Comorbidity Index (CCI, excluding hematologic malignancies) of 1.6 (2.2) and 1.4 (1.8), respectively; hypertension (67.8% MCL / 67.7% CLL), other hematologic malignancies (48.9% MCL / 52.0% CLL), and infection (28.0% MCL / 31.4% CLL) were the most common comorbidities. Other common (i.e., ≥ 20%) conditions included anemia and neutropenia for the MCL cohort, and arrhythmia, fatigue/asthenia, atrial fibrillation (A-fib), anemia and thrombocytopenia for the CLL cohort. Over 60% of MCL and CLL acalabrutinib-treated patients were defined as high risk of A-Fib (Chyou, Hunter et al. 2015). In terms of prior Bruton's Tyrosine Kinase-inhibitor (BTKi) treatment, 37.9% of MCL and 64.7% of CLL patients had prior ibrutinib use. More prior ibrutinib users were defined as high risk A-Fib status at time of acalabrutinib start than patients without prior ibrutinib use, and prior ibrutinib users had a higher frequency of several comorbidities (e.g., hypertension, fatigue/asthenia; Table 1). Conclusions With the relatively recent approval, this is the first analysis of acalabrutinib use in clinical practice and description of characteristics of MCL and CLL patients being treated with this medication in the real world. Before initiating acalabrutinib, approximately one-third of MCL patients and two-thirds of CLL patients received ibrutinib (reasons for discontinuing ibrutinib were not explored). Although the overall comorbidity score was similar between patients with and without prior BTKi exposure, BTKi-naïve patients had a slightly lower frequency of high-risk A-Fib status at acalabrutinib initiation. Future studies are warranted to evaluate the treatment patterns of acalabrutinib and outcomes in the real-world setting. Disclosures Ryan: AstraZeneca: Employment, Equity Ownership. Burudpakdee:IQVIA: Consultancy. Zhao:IQVIA: Consultancy. Le:AstraZeneca: Employment, Other: Stocks. Near:IQVIA: Consultancy. OffLabel Disclosure: Acalabrutinib is an oral inhibitor of Bruton's Tyrosine Kinase. It was approved by the US Food and Drug Administration on October 31, 2017 for patients with mantle cell lymphoma (MCL) who have progressed on at least one prior therapy and is currently being evaluated in phase III trials for first-line MCL, first-line chronic lymphocytic leukemia (CLL), and relapsed/refractory CLL.

Description: Introduction: Treatment for chronic lymphocytic leukemia (CLL) has changed with the approval of novel agents, which have different toxicity profiles. The aim of the current analysis was to determine how incremental changes in efficacy and toxicity profile impact treatment selection among patients with CLL and oncologists. Methods: In this US-based study, oncologists and CLL patients completed an online survey that included a discrete choice experiment (DCE) to quantify preferences for first line (1L) treatment with novel agents. Self-reported data on oncologist and patient characteristics were also collected. In the DCE, respondents selected between hypothetical treatment profiles consisting of 8 attributes with varying levels. The attributes were selected based on the findings of qualitative interviews assessing treatment priorities among oncologists and patients. The attribute levels were abstracted from clinical trials and published literature (Table 1). Hierarchical Bayesian regression models were used to estimate preference weights for each attribute level. The preference weights were used to generate a base case hypothetical treatment profile, against which other hypothetical profiles varying in adverse event (AE) risk and 2-year progression-free survival (PFS) were evaluated to understand which attributes and levels drive treatment selection. The overall mean summed preference weight for the collective set of alternative profiles was then compared with the base case, with higher positive values indicating the more preferred profile. Results: Oncologists (N=151) reported a mean of 16.3±7.0 years in practice (Table 2). Most practiced in a community setting (72%) and in a major metropolitan/urban area (64%). Among patients (N=220), median age was 56.0 years, with a mean disease duration of 2.0±3.1 years at time of study (Table 2). Most patients were in or had completed at least 1L therapy (68%). Figure 1 illustrates the impact of changing various attribute levels on the overall preference of an alternative profile, relative to a base case profile. Decreasing 2-year PFS from 95% to 75% (Profile A) and reducing the risks of atrial fibrillation (A-fib) from 20% to 5% (Profile B) and infection from 30% to 7% (Profile C) had the greatest influence on treatment preferences for oncologists when holding all other attribute levels constant. Oncologists preferred the profile with reduced 2-year PFS and reduced risk of AEs (Profile G) to the base case profile, corresponding to a 45% difference in preference share. Similarly, for patients, reducing 2-year PFS from 95% to 75% (Profile A) and reducing the risks of infection from 30% to 7% (Profile C) and A-fib from 20% to 5% (Profile B) were most influential in treatment choice when all other attribute levels were held constant (Figure 1). However, patients preferred the base case profile with higher PFS and higher risk of AEs to Profile G, corresponding to a 38% difference in preference share. Conclusions: For oncologists and patients, decreasing 2-year PFS and reducing the risks of either A-fib or infection had the most influence on 1L treatment preference, relative to the base case in which 2-year PFS was the highest and the AE risks were set to the worst levels reported in literature for novel therapies. The pattern and direction of treatment preferences were generally consistent among oncologists and patients, relative to the base case, across all alternative profiles when individually examined. However, for patients, the positive impact of reducing the risk of AEs was outweighed by the negative impact of reducing PFS. Consequently, all other things being equal, patients preferred a 1L profile with higher PFS even if it came with higher AE risks. In contrast, oncologists were willing to accept a treatment with less efficacy in exchange for the most favorable safety profile. This difference may be due to a patient's lack of understanding of the potential severity of AEs or a physician's lack of awareness of the patient's treatment priorities. This is an area for future research and highlights the importance of oncologists explicitly communicating the known efficacy benefits and AE risks associated with each treatment option because these factors may influence patients' treatment choice in a way that differs from their own. Disclosures Ryan: AstraZeneca: Current Employment, Current equity holder in private company. Le:AstraZeneca: Current Employment, Current equity holder in private company. Wahlstrom:AstraZeneca: Current Employment, Current equity holder in private company. Beusterien:Kantar: Other: Employee of Kantar, which received funding from AstraZeneca to conduct this study. Will:Kantar: Other: Employee of Kantar, which received funding from AstraZeneca to conduct this study. Maculaitis:Kantar: Other: Employee of Kantar, which received funding from AstraZeneca to conduct this study. Leblanc:UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding.

Description: Introduction: Since its approval in 2014, ibrutinib has replaced chemotherapy to become a preferred therapy for CLL patients. Real-world studies of ibrutinib in CLL patients have shown higher rates of discontinuations due to adverse events (AEs; 14-23%) compared with data from the early clinical trials of ibrutinib (4-9%). Similarly, dose reduction rates due to AEs in the real-world studies were 22-28%, vs 9% in the ibrutinib package insert. These real-world studies have been mostly focused on the academic setting or based on registry data. This study was part of an initiative to collect chart-review data from an academic practice and broader community networks, using an identical protocol to describe ibrutinib dose reductions and discontinuations in CLL patients. Methods: This was a multicenter, retrospective, chart review study of CLL patients and treated with ibrutinib. De-identified data were pooled from 2 community networks and 1 academic practice. Each community network agreed to contribute 50 patients on ibrutinib to the pooled data. To minimize potential bias, the patients were randomly selected from all the ibrutinib-treated patients in each network. All patients meeting inclusion criteria from the academic site were included. Inclusion criteria were: confirmed diagnosis of CLL, initiation of ibrutinib between March 2014 and June 2019, and ≥18 years of age at the initiation of therapy. Patients were excluded if they were actively receiving therapy for other primary cancers or were enrolled in a clinical trial of ibrutinib during the study period. Index date was defined as the date of ibrutinib initiation, and patients were followed for a minimum of 6 months. Variables collected included: patient demographics, clinical and treatment characteristics, molecular profiles, and reasons for dose reduction and discontinuation. Descriptive statistics were used to summarize the results. Results: 180 CLL Patients were included in this analysis. Of these, 56 (31%) patients received ibrutinib in the first line (1L) and 124 (69%) patients received ibrutinib in a relapsed/refractory (R/R) line. Over half (56%) of patients were treated in a community setting. Baseline demographic and clinical characteristics are shown in Table 1. 1L Ibrutinib patients had a median follow-up of 26 months. Twenty-five percent of patients (n=14) experienced at least one dose reduction, mainly due to AEs (n=11, 79%) (Figure 1). There was no single AE primarily responsible for dose reduction (Table 2). Treatment discontinuations were reported in 20% of patients, and they were more commonly due to AEs (73%) than disease progression (9%). Similarly, a variety of AEs led to discontinuations (Table 2). Median time to the first dose reduction for 1L patients was 9.9 months. Among patients who discontinued ibrutinib, median duration of treatment (DOT) was 15 months; with median DOT of 6 months for those who discontinued because of AEs and 28.9 months for those who discontinued because of progression. R/R Ibrutinib patients had a median follow up of 28.5 months. About a quarter (27.5%, n=34) of patients experienced at least 1 dose reduction, mainly due to AEs (n=30 [88%]) (Figure 1). The most common AEs leading to the first dose reductions were gastrointestinal (GI) disorder (43%), fatigue (23%), , and arthralgia/myalgia/musculoskeletal pain (17%) (Table 2). Treatment discontinuation was reported in 40% of patients, with over half due to AEs (58%) rather than disease progression (18%). The most common AEs leading to discontinuation were GI disorders (31%), atrial fibrillation (24%), and infections (21%) (Table 2). Median time to the first dose reduction in R/R patients was 3.1 months. Among patients who discontinued ibrutinib, median DOT was 9 months; with median DOT of 6 months for those who discontinued because of AEs and 30.2 months for those who discontinued because of progression. Conclusions: Dose reductions and discontinuations were frequent in CLL patients receiving ibrutinib in routine clinical practice. Compared with ibrutinib clinical trial data at a similar follow-up time, AEs were the most common reasons leading to discontinuation of ibrutinib rather than disease progression. The rates of dose reduction and discontinuations due to AEs in our study were higher than in clinical trials and were consistent with other real-world studies, indicating similar patterns in both community and academic settings. Disclosures Hou: Verastem: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Other: PI; AbbVie: Consultancy, Other: PI; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ryan:AstraZeneca: Current Employment, Current equity holder in private company. Du:AstraZeneca: Other: Grant. Fang:AstraZeneca: Other: Grant. Marks:Sanofi: Research Funding. Page:AstraZeneca: Other: Grants. Peng:AstraZeneca: Other: Grant. Szymanski:AstraZeneca: Current Employment, Other: Stockholder. Le:AstraZeneca: Current Employment, Current equity holder in private company.