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Optimal treatment of chronic lymphocytic leukemia (CLL) remains unclear. The Connect CLL Registry, a United States–based multicenter prospective observational cohort study, enrolled 1494 patients between 2010 and 2014 from predominantly community-based settings. Patients were grouped by line of therapy (LOT) at enrollment. With a median follow-up of 46.6 months (range, 0-63.0 months), median overall survival (OS) was not reached in LOT1, 63.0 months (95% confidence interval [CI], 46.0-63.0 months) in LOT2, and 38.0 months (95% CI, 33.0-47.0 months) in LOT≥3. Bendamustine and rituximab (BR; 33.5%); fludarabine, cyclophosphamide, and rituximab (FCR; 21.4%); and rituximab monotherapy (18.5%) were the most common regimens across LOTs. Median event-free survival (EFS) was similar in patients treated with BR (59.0 months) and FCR (55.0 months) in LOT1; median OS was not reached. In multivariable analysis, BR or FCR vs other treatments in LOT1 was associated with improved EFS (hazard ratio [HR], 0.60; P < .0001) and OS (0.67; P = .0162). Using the Kaplan-Meier product limit, ibrutinib vs other treatments improved OS in LOT2 (HR, 0.279; P = .009), LOT3 (0.441; P = .011), and LOT≥4 (0.578; P = .043). Prognostic modeling of death at 2 years postenrollment identified 3 risk groups: low (mortality rate, 6.2%), medium (14.5%), and high (27.4%). The most frequent adverse events across LOTs were pneumonia (11.6%) and febrile neutropenia (6.2%). These data suggest that advantages of LOT1 FCR over BR seen in clinical trials may not translate to community practice, whereas receiving novel LOT2 agents improved outcomes. This trial was registered at www.clinicaltrials.gov as NCT01081015.

Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect® MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2012-2016) of 3011 patients with NDMM, we identified prognostic variables for OS via the multivariable analysis of baseline patient characteristics in Cohort 1 (n = 1493) and developed a tool to examine individual outcomes. Factors associated with OS (n = 1450 treated patients; P < 0·05) were age, del(17p), triplet therapy use, EQ-5D mobility, International Staging System stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status and serum creatinine, which were used to create survival matrices for 3- and 5-year OS. The model was internally and externally validated using Connect MM Cohort 2 (Harrell's concordance index, 0·698), MM-015 (0·649), and the phase 3 FIRST (0·647) clinical trials. This novel prognostic tool may help inform outcomes for NDMM in the era of triplet therapy use with novel agents.

Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P < .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.

Introduction: Non-Hodgkin lymphoma (NHL) constitutes ~40% of hematologic malignancies and, in 2020, resulted in 19,940 deaths in the USA. The most common NHL subtypes are diffuse large B-cell lymphoma (DLBCL), including primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma (FL). Although a majority of patients respond to standard-of-care therapy, many patients with NHL eventually relapse, highlighting the need for additional treatments. Real-world data regarding the safety and efficacy of emerging therapies in the relapsed/refractory (R/R) population, and the association between treatment patterns and patient outcomes, are limited. These data could provide unique insights to clinical and health-related quality of life (HRQoL) outcomes in patients with DLBCL, FL, or PMBCL treated with emerging therapies, especially novel options such as chimeric antigen receptor (CAR) T cell therapies. Methods: The Connect ® Lymphoma Disease Registry (NCT04982471) is a US-based, multicenter, prospective observational cohort study of patients with R/R NHL (DLBCL, FL, and PMBCL). Approximately 2100 patients ≥ 18 years of age from ~200 community oncology (~80%) or academic (~20%) sites will be enrolled over a ~3-year period. Patients with histologically confirmed NHL subtypes will be enrolled into 1 of 4 cohorts: first R/R DLBCL, second R/R DLBCL, first R/R FL, or first R/R PMBCL (Figure). Patients will be required to have begun second- (first R/R) or third- (second R/R) line systemic treatment within 60 days prior to enrollment. Patients receiving treatment for any active malignancy other than DLBCL, FL, or PMBCL at the time of enrollment, or who are diagnosed with any other malignancy in the 6 months prior to enrollment, will be excluded. All treatment and management decisions will be determined by the practicing clinicians. Patients may undergo hematopoietic stem cell transplantation, CAR T cell therapy, or other treatments at other sites while participating in this study. Patients will be followed from enrollment for up to 5 years or until death, withdrawal of consent, loss to follow-up, or study termination, whichever occurs first. Data collection will occur at enrollment (baseline) and then every ~3 months. The main objectives of the Connect ® Registry are to describe patient characteristics, practice patterns, and factors associated with treatment choice, sequencing, and effectiveness in NHL subtypes. Secondary objectives include describing treatment regimen safety, patient-reported outcomes (PROs) including HRQoL, and healthcare resource utilization outcomes. Exploratory objectives include tumor and blood biomarker evaluation and understanding the availability of social support and its impact on long-term treatment decision-making. Case report forms will be used to collect clinical and treatment data, including baseline demographics, clinical characteristics, treatment details and response, and socioeconomic factors. Outcome measures for efficacy will be progression-free survival, event-free survival, objective response rate, time to next treatment, and overall survival. The availability of social support will be assessed via a specific questionnaire administered at baseline. General (EQ-5D-5L) and disease-specific (FACT-Lym) questionnaires will also be administered. Patients may also optionally agree to release tumor biopsies and blood samples for biomarker analysis. Clinicians will be required to report serious adverse events (AEs), secondary primary malignancies, and confirmed COVID-19 infections within 24 hours. Non-serious AEs of interest include grade 1-3 cytokine release syndrome, grade 1-3 neurotoxicity, grade 3 colitis, grade 3 arrhythmia, grade 3 hemorrhage. Other AEs of interest to be collected include grade 3 hypogammaglobulinemia, prolonged grade 3 cytopenia, and grade 3 infections. Data collected in the Connect ® Registry will increase understanding of the association between emerging therapies and patient outcomes for R/R DLBCL, FL, and PMBCL. Study support: Bristol Myers Squibb Figure 1 Figure 1. Disclosures Flowers: Amgen: Research Funding; Janssen: Research Funding; Biopharma: Consultancy; Ziopharm: Research Funding; Burroughs Wellcome Fund: Research Funding; Nektar: Research Funding; Karyopharm: Consultancy; Iovance: Research Funding; Allogene: Research Funding; AbbVie: Consultancy, Research Funding; Cellectis: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; BeiGene: Consultancy; Kite: Research Funding; EMD: Research Funding; Genentech/Roche: Consultancy, Research Funding; Morphosys: Research Funding; Adaptimmune: Research Funding; Novartis: Research Funding; Epizyme, Inc.: Consultancy; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Acerta: Research Funding; 4D: Research Funding; Denovo: Consultancy; Celgene: Consultancy, Research Funding; Guardant: Research Funding; Genmab: Consultancy; Gilead: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; SeaGen: Consultancy; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Takeda: Research Funding; National Cancer Institute: Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding. Andorsky: Celgene/Bristol Myers Squibb: Research Funding; AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; AstraZeneca: Other: served on steering committees; Epizyme: Research Funding; AbbVie: Research Funding. Burke: SeaGen: Consultancy, Speakers Bureau; X4 Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Verastem: Consultancy; AstraZeneca: Consultancy; MorphoSys: Consultancy; Adaptive Biotechnologies: Consultancy; Roche/Genentech: Consultancy; Epizyme: Consultancy; Kura: Consultancy; AbbVie: Consultancy; Beigene: Consultancy, Speakers Bureau; Kymera: Consultancy. Cerhan: Genentech: Research Funding; NanoString: Research Funding; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; Regeneron Genetics Center: Other: Research Collaboration. Grinblatt: Astellas Pharma, Inc.: Consultancy; Bristol Myers Squibb: Consultancy; Astra Zeneca: Consultancy; AbbVie: Consultancy. Toomey: Bristol Myers Squibb: Consultancy. Zelenetz: Gilead: Honoraria, Research Funding; Verastem: Honoraria; Novartis: Honoraria; MEI Pharma: Honoraria, Research Funding; SecuraBio: Honoraria; Abbvie: Honoraria, Research Funding; MorphoSys: Honoraria; Pharmacyclics: Honoraria; AstraZeneca: Honoraria; LFR: Other; Genentech/Roche: Honoraria, Research Funding; NCCN: Other; MethylGene: Research Funding; Beigene: Honoraria, Other, Research Funding; BMS/Celgene/JUNO: Honoraria, Other; Amgen: Honoraria; Gilead: Honoraria; Janssen: Honoraria. Sullivan: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Flick: Bristol Myers Squibb: Current Employment. Kiselev: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Kaplan: Bristol Myers Squibb: Current Employment. Ahn: Bristol Myers Squibb: Current Employment.

Context MF is a life-threatening type of myeloproliferative neoplasm (MPN) with significant morbidity and mortality. Current treatments aim to manage symptoms, improve anemia, and delay progression to acute myeloid leukemia (AML); however, limited real-world data hinder understanding of the safety and effectiveness of emerging therapies and the association between treatment patterns and patient outcomes. Objective To examine the effectiveness and safety of different therapeutics, treatment patterns, clinical outcomes, and patient-reported outcomes (PROs) in patients with MF or MF-related cytopenias. Design The Connect® Myeloid Disease Registry (NCT01688011; formerly Connect® MDS/AML Disease Registry) is a large, US, multicenter, prospective study of patients with newly diagnosed AML or myelodysplastic syndromes (MDS; Steensma et al. BMC Cancer 2016). A new cohort of patients diagnosed with MF began enrollment in February 2021. Patients Eligible patients are ≥18 years of age, must have an MF diagnosis (primary or secondary MF) and have initiated therapy ≤60 days prior to informed consent. 800 patients (n=400 patients receiving first active systemic treatment for MF and n=400 patients receiving treatment for MF-related cytopenias) will be enrolled at 200–250 sites. Patients with MDS/MPN overlap syndromes are also eligible. Patients who have a suspected or proven juvenile myelomonocytic leukemia diagnosis or are currently enrolled in any interventional clinical trial where the investigational product cannot be identified are not eligible. Main Outcome Measures All diagnoses, treatments, and laboratory testing are at the discretion of the treating physician, in accordance with standard clinical practice at each site. Health status, clinical response (by MFSAF, spleen size, transfusion burden, and bone marrow biopsy), overall survival, adverse drug reactions, serious adverse events (AEs), and protocol-defined AEs of interest will be collected. PRO data will be assessed using the MFSAF V.4, FACT-An, and EQ-5D-3L questionnaires. Patients may consent to an optional biomarker tissue sub-study. Patient data will be reported at baseline and quarterly for ≤5 years or until early termination, withdrawal, or death. Conclusions Data collected in the MF cohort of the Registry will increase understanding of the clinical effectiveness, safety, and PRO of current treatment strategies for patients with MF. This is a BMS-sponsored study.

Chemoimmunotherapy for chronic lymphocytic leukemia (CLL) promotes clonal evolution of aggressive clones, which in some patients may lead to early progression of disease (POD). We studied the prognostic value of early POD in a cohort of patients with CLL enrolled between 2010 and 2014 in the Connect CLL Registry. Overall, 829 eligible patients receiving first-line therapy were categorized into 3 groups: early POD (progression

Introduction: Outcomes among pts with AML have improved over the last 20 years with the introduction of novel, targeted, and reformulated chemotherapy agents, as well as the optimization of allogeneic hematopoietic stem cell transplantation (HSCT) strategies. The majority of pts, however, relapse after achieving remission, particularly those who are ineligible for or choose not to proceed to HSCT. To date, there is limited information available characterizing real-world Tx patterns of therapies offered to pts with AML who achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi) and the subsequent impact on pt outcomes. Therefore, we analyzed data on post-remission therapy, including use of maintenance therapy, in pts with ND AML aged ≥ 55 years from the Connect® MDS/AML Disease Registry (NCT01688011), a large, multicenter, prospective observational cohort study of US pts with AML. Methods: Demographics, clinical characteristics, and Tx data were collected at the time of enrollment, and every 3 months during follow-up for pts enrolled in the Registry from Dec 2013 to the data cutoff for this analysis of Mar 2020. Pts were categorized as having received first-line therapy (intensive or non-intensive induction) or supportive care (including no Tx), based on medical records provided within 45 days of initial AML diagnosis. For pts achieving CR/CRi following induction, post-remission Tx was defined as: prolonged therapy (ongoing, non-intensive regimen similar to induction, administered until disease progression), consolidation (post-remission intensive chemotherapy), maintenance (non-intensive therapy administered for a prolonged period of time, with agent(s) not used during induction), and HSCT. Overall survival (OS), calculated from the time of CR/CRi, was determined using the Kaplan-Meier method. Results: As of Mar 2020, 638 pts with AML (median age 71 years; range 55−97) were enrolled in the Registry. The proportion of pts treated at community/government vs academic sites was 59% and 41%, respectively. A total of 587 ND AML pts had complete Tx data for analysis (evaluable population). Baseline characteristics are shown in the Table. Of the evaluable population, 299 (51%) received intensive induction, 280 (48%) non-intensive induction, and 8 (2%) supportive care only. A total of 233 (40%) evaluable pts achieved first CR/CRi following induction therapy: 183 received intensive induction and 50 received a non-intensive regimen. Tx patterns for pts achieving CR/CRi are shown in the Figure. Among the 587 evaluable pts, 108 (18%) received HSCT; of these, 81 (75%) proceeded to HSCT after achieving first CR/CRi with induction (77 [95%] received intensive induction, 4 [5%] received non-intensive induction) ± consolidation therapy. The most frequent reasons for transplant ineligibility were age (64%), comorbidities (49%), not achieving remission (30%), and Eastern Cooperative Oncology Group performance status (23%). Median OS was 48.2 months for pts in first CR/CRi who had HSCT vs 21.0 months for pts in first CR/CRi who did not. Among the 233 pts achieving CR/CRi, 51 (22%) received maintenance therapy: 36 (15%) had maintenance after induction ± consolidation, and 15 (6%) received maintenance therapy post HSCT. Median duration of maintenance was 112 days (range 3-786). Conclusions: Among pts with ND AML in the Connect® MDS/AML Disease Registry who achieved CR/CRi, more received an intensive induction regimen vs a non-intensive regimen. Additional time will be needed to accurately evaluate the impact of novel non-intensive induction regimens (e.g. IDH1/2 inhibitors, venetoclax, FLT3 inhibitors), which have shown improved remission rates and OS outcomes compared with prior low-intensity regimens. Fewer than one third of pts who achieved first CR/CRi following induction ± consolidation proceeded to HSCT, and those transplanted in first CR/CRi showed improved OS vs those without HSCT. These results suggest that real-world practices may tend to select younger, more fit pts with AML as candidates for intensive induction therapy and HSCT. Given that maintenance is not a widely established practice in AML, only 22% of pts in remission received maintenance therapy as a means to improve outcomes. This may change with the approval of novel therapies in the AML maintenance setting, which have the potential to prolong remission, delay relapse, and prolong OS following CR/CRi. Disclosures Roboz: Agios: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Array BioPharma: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Eisai: Consultancy; Jazz: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Actinium: Consultancy; Argenx: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; AstraZeneca: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Takeda: Consultancy; Trovagene: Consultancy; Cellectis: Research Funding; Jasper Therapeutics: Consultancy; Epizyme: Consultancy; Helsinn: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Astex: Consultancy; Amphivena: Consultancy. Cogle:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aptevo Therapeutics: Research Funding. Pollyea:Pfizer: Consultancy; Celgene/BMS: Consultancy; Takeda: Consultancy; Daiichi Sankyo: Consultancy; Abbvie: Consultancy, Research Funding; Syros: Consultancy; Syndax: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Janssen: Consultancy; 47: Consultancy, Research Funding; Agios: Consultancy; Glycomimetics: Other. Abedi:AbbVie, BMS, Gilead Sciences, Seattle Genetics, Takeda: Speakers Bureau; BMS, Gilead Sciences: Research Funding. Thompson:Doximity: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Synapse Precision Medical Council: Other: Travel expenses; AIM Specialty Health, BMS, GlaxoSmithKline, Takeda, Via Oncology: Membership on an entity's Board of Directors or advisory committees. Nifenecker:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Flick:Bristol Myers Squibb: Current Employment. Kiselev:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Louis:Bristol Myers Squibb: Ended employment in the past 24 months. Little:Bristol Myers Squibb: Current Employment. Erba:AbbVie, Daiichi Sankyo, Forma, ImmunoGen, Jazz Pharmaceuticals, MacroGenics, Novartis, PTC: Research Funding; AbbVie, Agios, Celgene, Incyte, Jazz Pharmaceuticals, and Novartis: Speakers Bureau; AbbVie, Agios, Amgen, Astellas, Celgene, Daiichi Sankyo, Glycomimetics, ImmunoGen, Incyte, Jazz Pharmaceuticals, MacroGenics, Novartis, and Pfizer: Consultancy; Glycomimetics: Other: member of Scientific Steering Committee; Celgene: Other: chair of the Scientific Steering Committee; Covance (AbbVie): Other: chair of the Independent Review Committee.

Hematopoietic stem cell transplantation (HSCT) is often indicated and formal transplant referral guidelines exist for pts with AML and HR MDS. However, the proportion of transplant-eligible pts not referred is largely unknown. We therefore assessed HSCT referral patterns, including potential barriers to referral, in pts with ND MDS and AML enrolled in the Connect® MDS/AML Disease Registry (NCT01688011), a large, US, multicenter, prospective observational cohort study of pts with ND AML (aged ≥ 55 years) or MDS (aged ≥ 18 years). We evaluated pt data, including transplant referral decisions collected at enrollment and every 3 months, from pts enrolled from Dec 2013 to Jul 2019. HR MDS and AML pts were included; AML pts were grouped by ELN 2010 risk groups into IR AML (Int-1 and Int-2 risk), or AR AML (adverse risk). Differences in transplant referral rates were assessed using a chi-square t-test (significance P

BACKGROUND: Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs. This article describes a project of the Clinical Trials Transformation Initiative (CTTI) intended to help clinical trials researchers determine when a registry could potentially serve as the platform for the conduct of a clinical trial. METHODS: Through a review of registry-embedded clinical trials and commentaries, semi-structured interviews with experts, and a multi-stakeholder expert meeting, the project team addressed how to identify and describe essential registry characteristics, practices, and processes required to for conducting embedded clinical trials intended for regulatory submissions in the United States. RESULTS: Recommendations, suggested practices, and decision trees that facilitate the assessment of whether a registry is suitable for embedding clinical trials were developed, as well as considerations for the design of new registries. Essential registry characteristics include relevancy, robustness, reliability, and assurance of patient protections. CONCLUSIONS: The project identifies a clear role for registries in creating a sustainable and reusable infrastructure to conduct clinical trials. Adoption of these recommendations will facilitate the ability to perform high-quality and efficient prospective registry-based clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43441-020-00185-5) contains supplementary material, which is available to authorized users.

7040 Background: At diagnosis, disease risk and transfusion burden (TB) can impact HRQoL in pts with MDS. The impact of disease status and higher transfusion requirements on HRQoL has not been well studied. We used data from the Connect Myeloid Disease Registry, an ongoing, prospective, observational cohort study that includes adult pts with lower-risk (LR) and higher-risk (HR) MDS, to investigate factors influencing baseline (BL) and subsequent HRQoL. Methods: BL and Month 6 (M6) data from pts enrolled from Dec 12, 2013 to Mar 6, 2020 (data cutoff) were analyzed. Pts were stratified by International Prognostic Scoring System (IPSS) risk (LR, HR), treatment (Tx) within 45 days post-enrollment (no Tx, best supportive care [BSC], active Tx), and TB 16 weeks post-BL (non-transfusion dependent [NTD], low TB [LTB]; 1−3 transfusions, high TB [HTB]: ≥4 transfusions). Pts completed EQ-5D, FACT-An trial outcome index (TOI), and FACT-Fatigue (FACT-F) questionnaires at BL and quarterly thereafter. Clinically meaningful change, based on minimally important differences, was defined as a change of ±0.07 for EQ-5D, ±6 for FACT-An TOI, and ±3 for FACT-F. Results: At data cutoff, 830 (489 LR, 341 HR) pts were enrolled. Median age was 74 years. 278 pts received no initial Tx, 161 BSC, and 378 active Tx. At BL, 470 were NTD, 197 LTB, and 163 HTB. Of 670 pts still on-study at M6, 462 completed the questionnaires at both BL and M6. At BL , clinically meaningful differences were observed in FACT-An TOI and FACT-F scores, but not EQ-5D, between LR- and HR-MDS and the Tx subgroups . From BL to M6, no clinically meaningful changes were observed in mean scores for each questionnaire. For the TB subgroups, meaningful differences were observed at BL in FACT-An TOI and FACT-F scores, but not EQ-5D (Table). From BL to M6, meaningful decreases in scores were reported by 26%, 30%, and 35% of NTD, LTB, and HTB pts in EQ-5D, 41%, 43%, and 48% for FACT-An TOI, and 40%, 42%, and 48% for FACT-F; increases were reported by 19%, 19%, and 20% pts for EQ-5D, 31%, 32%, and 39% for FACT-An TOI, and 30%, 39%, and 40% for FACT-F. Conclusions: This preliminary analysis suggests that pts with HR-MDS, and transfusion-dependent pts, generally had worse HRQoL at BL, providing further support to initiating active Tx in pts with TB. Possible limitations of the analysis are lower completion rates in pts with more severe disease, and EQ-5D may not capture changes in these subgroups at M6. A longer follow-up may help delineate the impact of Tx on HRQoL assessments in pts with MDS. Clinical trial information: NCT01688011. [Table: see text]

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice.

Context: Molecular genetic testing is an important diagnostic tool for MDS. WHO MDS classification criteria were updated in 2016; how they are implemented in practice is unclear. Our knowledge of molecular testing in elderly patients is limited. Objective: To compare testing patterns in elderly (≥80 years) and younger ( Design: Baseline characteristics and laboratory data were collected from patients enrolled from Dec 12, 2013 to data cutoff Dec 13, 2019 in the Connect® MDS/AML Disease Registry ( NCT01688011 ), an ongoing, US, multicenter, prospective observational cohort study of patients with newly diagnosed MDS (aged ≥18 years) or AML (aged ≥55 years). Testing patterns were compared between elderly and younger MDS patients. Results: 234/800 (29.3%) MDS patients were aged ≥80 years and 566/800 (70.7%) Conclusions: Although molecular testing rates have increased since 2017, testing rates for elderly MDS patients remained lower than for younger patients. Education focused on increasing testing rates in elderly patients is needed to ensure appropriate care. The study was supported by Bristol-Myers Squibb.

Purpose Bevacizumab used in combination with first-line chemotherapy confers an overall survival (OS) benefit for patients with non-squamous non–small-cell lung cancer (NSCLC). This analysis from the ARIES observational cohort study (OCS) was initiated to evaluate the effect of bevacizumab use beyond disease progression (BBP) on clinical outcomes in patients with NSCLC receiving first-line treatment with bevacizumab and chemotherapy. Methods The ARIES OCS prospectively enrolled patients from 2006 to 2009 in the United States who had advanced non-squamous NSCLC, received bevacizumab with chemotherapy in the first-line setting, and survived progressive disease (PD). A dichotomous landmark analysis examined post-PD OS (ppOS) in patients who received BBP versus no BBP within 30 days post PD. A time-dependent Cox model assessed the effect of cumulative BBP exposure on ppOS. Results The ARIES OCS enrolled 1967 patients with first-line NSCLC; 1358 patients had first PD and were alive at the 30-day landmark (351 patients with BBP and 1007 patients with no BBP). The landmark analysis showed that BBP was associated with a lower risk of death (BBP versus No-BBP); hazard ratio [HR], 0.75; 95% confidence interval 0.65–0.86. In the cumulative exposure analysis of 1461 patients who had PD, HRs for ppOS decreased by approximately 4% for each additional 21-day interval of bevacizumab received. Protocol-specified bevacizumab-select adverse events occurred in 14% of BBP patients. Conclusions BBP was associated with a lower risk of death in patients with NSCLC treated with first-line bevacizumab and chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.

A ‘watch-and-wait’ strategy is recommended for most patients with early-stage chronic lymphocytic leukemia (CLL) prior to treatment initiation. In the Connect® CLL registry, a prospective observati...

Background The treatment landscape for multiple myeloma (MM) has undergone recent changes with the regulatory approval of several new therapies indicated for second- and later-line disease. Using data from Connect MM, the largest multisite, primarily community-based, prospective, observational registry of MM patients in the United States, selection of second-line treatments was evaluated during a 5-year period from 2010 to 2016. Patients and Methods Eligible patients were aged ≥ 18 years, had newly diagnosed MM ≤ 2 months before study entry, and were followed for up to 8 years. Patients who received ≥ 2 lines of therapy were analyzed. "Tepee" plots of stacked area graphs differentiated treatments by color to allow visualization of second-line treatment trends in MM patients. Results As of February 2017, 855 of 2897 treated patients had progressed to second-line treatment. Treatment selection was heterogeneous; shifting patterns of treatment choices coincided with the approval status of newer agents. The most common treatment regimens in the early part of the decade were lenalidomide and/or bortezomib, with or without dexamethasone, with increasing use of newer agents (carfilzomib, pomalidomide, daratumumab, and elotuzumab) and triplet combinations over time. The influence of the baseline patient characteristics of age, history of diabetes, peripheral neuropathy, and renal function on treatment choice was also examined. Conclusion These findings indicate that community physicians are current in their MM management practices, with uptake of new drugs and acquaintance with results of randomized clinical trials using combinations almost concurrent with their regulatory approval and publication.

The performance of multiple myeloma (MM) therapies in a general patient population and specific eligibility criteria that might limit enrollment into randomized controlled trials (RCTs) have not been evaluated in depth. This study aimed to determine if improvements seen with MM therapies in RCTs are reflected in the general patient population and to identify eligibility criteria that can be modified to increase enrollment.The Connect MM Registry is a prospective observational cohort study of patients with newly diagnosed MM (NDMM) in the United States. Using common RCT exclusion criteria collected from 16 published studies, patients in the registry were categorized according to their eligibility for inclusion in RCTs.On the basis of common criteria, 563 of 1406 of registry patients (40.0%) are ineligible for RCTs. Criteria leading to exclusion included M-protein ≤ 1.0 g/dL (25.2%), creatinine2.5 mg/dL (13.9%), low absolute neutrophil count (10.0%), and low hemoglobin (9.6%). Significantly more RCT-ineligible versus RCT-eligible patients had hypercalcemia (11.0% vs. 5.5%), elevated creatinine levels (38.9% vs. 6.2%), low hemoglobin levels (59.5% vs. 39.5%), or International Staging System stage III disease (40.1% vs. 22.1%; P .001 for all comparisons). RCT-ineligible patients had a lower 3-year survival rate than RCT-eligible patients (63% vs. 70%). The incidence of serious adverse events was similar between groups.Of patients with NDMM enrolled in the Connect MM Registry, 40% are ineligible for RCTs. This study provides insight into potential modifications of standard eligibility criteria that can lead to improved RCT design and accelerated enrollment.

Background Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is > 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. Methods The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010–2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan–Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. Results A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p

Background: Diagnosing and risk stratifying MDS requires an integrated approach including morphologic, cytogenetic, and molecular genetic assessments to inform treatment decisions and aid prognostication. The WHO classification criteria for diagnosis of MDS were updated in 2016 (Arber DA, et al. Blood. 2016;127:2391-405) with specific recommendations; however, the impact of these updates on clinical practice patterns is unclear. We investigated testing patterns for pts with ND MDS treated in predominantly community- and government-based centers in the Connect® MDS/AML Registry and compared these practices with the WHO 2016 criteria. Methods: The Connect® MDS/AML Disease Registry (NCT01688011) is a large, US, multicenter, prospective observational cohort study of pts with ND acute myeloid leukemia (AML; aged ≥ 55 years) or MDS (aged ≥ 18 years). Baseline demographics, disease characteristics, and laboratory testing parameters were collected on MDS pts at enrollment to the Registry from December 2013 to March 2019. Pts were classified according to the International Prognostic Scoring System (IPSS) as having lower-risk MDS (LR-MDS; IPSS Low- or Intermediate-1-risk MDS) or higher-risk MDS (HR-MDS; IPSS Intermediate-2- or High-risk MDS). Differences in testing rates at enrollment between LR- and HR-MDS pts were assessed using a chi-square test with P < 0.05 considered statistically significant. Concordance with the recommendations of the WHO 2016 criteria, including frequency of SF3B1 testing, was assessed. Results: As of March 8, 2019, 694 pts with MDS were enrolled in the Registry; 392 (56.5%) with LR-MDS and 302 (43.5%) with HR-MDS. Median age was 75.0 vs 73.0 years, 66.3% vs 64.9% were male, and 70.6% vs 75.6% were insured by Medicare/Medicaid. There was a significant difference in bone marrow blast enumeration method between LR- and HR-MDS pts; the most common method was manual differential (75.9% vs 72.1%), followed by immunohistochemistry (IHC) (11.5% vs 21.5%) (P = 0.002). The mean (standard deviation) number of cells counted on manual differential was 361.7 (151.3) in LR-MDS pts and 348.2 (163.6) in HR-MDS pts. This was not significantly different between pt groups, but was below the recommended 500 cells. Presence of ring sideroblasts (RS) was more common in LR- than HR-MDS pts (39.8% vs 34.1%; P = 0.02); median percentage of RS was also higher in LR- than HR-MDS pts (25.0% vs 7.5%; P < 0.0001). The majority of pts underwent complete cytogenetic analysis at baseline; 97.4% of LR- and 95.7% of HR-MDS pts. Flow cytometry testing to assess cell lineage was widely done; 97.0% of HR-MDS pts and 93.6% of LR-MDS pts. To assess changes in diagnostic testing patterns following publication of the WHO 2016 criteria, LR- and HR-MDS pts were grouped based on their date of enrollment: pts enrolled prior to January 1, 2017, and pts enrolled from January 1, 2017 onward. Molecular testing rates increased in pts enrolled after January 1, 2017, from testing rates seen prior to 2017, in LR- and HR-MDS pts; however, testing rates remained < 40% (Table). Testing rates for specific mutations were higher in pts enrolled after January 1, 2017 than in those enrolled prior to 2017. In parallel with overall testing rates, testing rates for SF3B1 were also higher in pts enrolled after January 1, 2017; however, they remained at approximately 50% in these pts. During this time, rates of fluorescence in situ hybridization testing decreased by 36.1% and 26.0% in HR- and LR-MDS pts, respectively. Conclusions: In this analysis from the Connect® MDS/AML Registry, increased SF3B1 testing rates were observed following the publication of the WHO 2016 criteria, suggesting uptake of this recommendation by physicians. The increase in testing rates for other specific mutations associated with targeted therapies coincides with the approval of these new therapies by the US FDA. However, further education to increase molecular testing rates for specific mutations, improve prognostication, as well as to ensure the appropriate use of targeted therapies is required. The use of IHC rather than manual differential for blast enumeration, as recommended by the WHO, and the significant difference in enumeration method between LR- and HR-MDS pts, may be due to higher levels of fibrosis in HR pts and poor-quality aspirates rather than a lack of awareness of the recommendations; however, the recommended counting of 500 cells was not performed in all pts. Disclosures George: Novartis: Honoraria; Blueprint Medicines: Consultancy; Deciphera: Consultancy; Allakos: Consultancy. Garcia-Manero:Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Komrokji:Incyte: Consultancy; DSI: Consultancy; Celgene: Consultancy; Agios: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Alexion: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Speakers Bureau. Savona:Boehringer Ingelheim: Patents & Royalties; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Speakers Bureau. Sekeres:Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Steensma:Stemline: Consultancy; Onconova: Consultancy; Aprea: Research Funding; Arrowhead: Equity Ownership; H3 Biosciences: Other: Research funding to institution, not investigator.; Astex: Consultancy; Summer Road: Consultancy; Pfizer: Consultancy. Flick:Celgene Corporation: Employment. Kiselev:Celgene Corporation: Employment, Equity Ownership. Louis:Celgene Corporation: Employment, Equity Ownership. Nifenecker:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene Corporation: Employment, Equity Ownership. Foucar:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Background. The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. Methods. The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan–Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. Results. In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX–bevacizumab (n = 968) or FOLFIRI–bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX–bevacizumab and FOLFIRI–bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI–bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88–1.21) and OS (HR, 0.95; 95% CI, 0.78–1.16) outcome as with FOLFOX–bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. Conclusions. In first-line mCRC patients, the FOLFOX–bevacizumab and FOLFIRI–bevacizumab regimens were associated with similar treatment patterns and clinical outcomes.

300 Background: Establishing an accurate LOT definition in real-world data (RWD) oncology studies is critical for measuring the effects of treatments on outcomes, which informs decisions made by clinicians, regulators, and payers. However, measuring LOT in RWD analyses is challenging and varies across disease states. LOT is generally defined by treatment (tx) start and stop dates. When available, the date of disease progression (PD) can be used to enhance the LOT definition. We explored the analytical impact of varying LOT definitions on 2L survival outcomes. Methods: A retrospective analysis of patients (pts) with mPC treated in US community practices was conducted using the Flatiron Health EHR–derived database. Two algorithms were applied to define LOT: tx change or ≥ 60-day gap in tx (LOTtx) and tx change after first PD (LOTpd). The impact on 1L and 2L sample sizes as well as 2L overall survival (OS) and progression-free survival (PFS) were assessed. Results: 251 pts with an mPC diagnosis between 01 March and 31 October 2015, who initiated chemotherapy ≤ 60 days after mPC diagnosis, were analyzed. Applying the LOTtx definition, 121 pts received 1L tx only and 130 received a 2L tx. Using the LOTpd definition, 145 pts received 1L tx only and 105 received a 2L tx (12 pts were excluded due to unclear time of PD relative to tx). Applying these definitions to time-to-event analyses (from start of 2L therapy) revealed longer 2L OS with LOTtx vs LOTpd (n = 130 vs 105; median 2L OS [95% CI], 5.4 [4.1-7.4] versus 4.5 [3.7-7.3] mo) but similar 2L PFS (n = 122 vs 105; median 2L PFS [95% CI], 2.8 [2.3-3.5] versus 2.8 [2.3-3.6] mo). Conclusions: In this analysis, inclusion of PD in the LOT definition impacted 1L and 2L sample sizes and 2L survival results. In aggressive diseases like mPC, a 1-mo difference in OS estimates is clinically meaningful and may influence treatment decisions. The choice of LOT definition should be based on the research question at hand, available data, and the effort to decrease misclassification bias. Additional LOT definitions, with associated strengths and limitations, will also be presented.

Introduction: A number of treatment (Tx) options are available for ND AML pts including high-intensity (HI) chemotherapy ("7+3" regimen) followed by consolidation chemotherapy or allogeneic hematopoietic cell transplantation, low/intermediate-intensity (LI) therapies (low-dose cytarabine or hypomethylating agents), best supportive care (BSC), or no Tx. While data describing HCRU by AML pts informs health systems, clinicians, and pts of the requirements for managing AML pts, HCRU studies in this population are lacking. An analysis of ND AML pts from the Connect® MDS/AML Disease Registry was conducted to examine HCRU in pts receiving different Tx modalities. Methods: The Connect MDS/AML Disease Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts in the USA with ND AML (aged ≥ 55) or myelodysplastic syndromes (aged ≥ 18). All interventions are conducted in accordance with physicians' standard of care. Pt demographics, disease characteristics, and Tx information were collected at screening and every 3 months from AML pts enrolled from December 2013 to March 2018. HCRU was assessed in ND AML pts according to Tx groups defined as HI, LI, BSC, or no Tx initiated ≤ 45 days post-diagnosis. Unplanned hospitalizations related to disease or Tx-related complications were assessed in all pts at 3 and 6 months post-enrollment. Response to Tx was analyzed in pts receiving HI and LI therapy only. Number of transfusion episodes (red blood cell or platelet) was calculated over 6 months post-enrollment, and at each month in pts receiving HI or LI therapy; data for partial months were excluded to accurately assess transfusion episodes/month. Results: A total of 434 AML pts, treated at 20 academic and 85 community/government centers, were included in the analysis. Median age was 70 years (range 55-92), 65% were male, and 83% were white. 95 (21.9%) pts received BSC/no Tx, 153 (35.3%) received LI therapy and 186 (42.9%) received HI therapy. A higher proportion of pts receiving HI therapy had ≥ 1 hospitalization compared with LI and BSC/no Tx groups (59.7% vs 49.0% vs 24.2%; P < 0.05). Mean number of hospitalization days/month in the HI, LI, and BSC/no Tx groups was 6.8 vs 5.7 vs 3.2 days, respectively. During the first 3 months of Tx, pts in the HI group spent a mean of 20.5 days in hospital vs 11.4 days for pts in the LI group, and 9.5 days for pts receiving BSC/no Tx. During the last 3 months of the study period, the number of hospitalization days decreased across all Tx groups to 10.4, 7.0, and 7.7 days, respectively. There were significant differences in mean monthly transfusion burden over the first 6 months of the study for pts in the HI and LI groups (4.9 vs 2.7 transfusion episodes/month; P < 0.01). During month 1 post-enrollment, the mean number of transfusion episodes in the HI group was 8.3 vs 3.4 in those receiving LI therapy (P < 0.01 after adjusting for insurance status). Over the 6-month study period, the transfusion rate decreased in both groups with a mean decrease of 6.3 and 1.8 transfusion episodes from month 1 to month 6 for HI and LI therapy, respectively (P < 0.01). At month 4, the transfusion rate in pts receiving HI therapy fell below that of the LI group (Figure), coinciding with the end or near completion of consolidation chemotherapy in the HI group. In logistic regression analyses, pts receiving HI therapy were significantly more likely to achieve complete remission (CR) vs pts receiving LI therapy, after adjusting for age, comorbidities, and disease risk (odds ratio = 4.2, 95% confidence interval 1.7-9.1; P < 0.01). Results from a sensitivity analysis, which excluded pts who had received a transplant, were consistent with the main analysis. Mortality rates were not significantly different between LI and HI groups at day 30 and day 60 but were at day 180 (P < 0.01; Table). Conclusions: These findings from the Connect MDS/AML Disease Registry highlight the level of HCRU in ND AML pts treated with different intensity therapies. While HCRU, as measured by transfusion burden and unplanned hospitalizations, was highest in the HI group, pts in the HI group were significantly more likely to achieve CR, and had lower mortality rates at a 180-day landmark. Higher HCRU rates during early Tx in the HI group are likely a reflection of cytopenia-related complications due to the highly myelosuppressive nature of HI regimens. Therefore higher HCRU during early therapy in the HI group may be offset by improved pt outcomes. Disclosures Abedi: BMS: Speakers Bureau; CIRM: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Erba:Astellas: Research Funding; Janssen: Research Funding; Janssen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Amgen: Research Funding; Pfizer: Consultancy, Other: grant; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Amgen: Research Funding; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Astellas: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Pfizer: Consultancy, Other: grant; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Takeda/Millenium: Research Funding; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; MacroGenics: Consultancy; Juno: Research Funding; Juno: Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Sandoz: Consultancy; Daiichi Sankyo: Consultancy; Janssen Pharmaceuticals: Consultancy; Orsenix: Consultancy; AbbVie: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Cellectis: Research Funding. Louis:Celgene: Employment; Cellmedica: Patents & Royalties. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Cogle:Celgene: Other: Steering Committee Member of Connect MDS/AML Registry.

7037Background: Historically, only about 40% of AML pts ≥ 65 y of age receive first-line therapy (1LTx) due to high adverse event and low 5-y survival rates. With the introduction of new agents to ...

8041Background: Real-world longitudinal data on tx sequencing & outcomes are limited. The Connect MM Registry is a US, multicenter, prospective observational cohort study designed to examine diagno...

The association between long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) and non-Hodgkin lymphoma (NHL) was examined using data collected between October 2001 and May 2004 in an ongoing population-based case-control study in the San Francisco Bay Area. NHL cases were identified using rapid case ascertainment and Surveillance, Epidemiology, and End Results registry data. Control participants were frequency-matched to cases by age, sex, and county of residence. Participants completed in-person interviews designed to measure potential NHL risk factors. Questions were asked regarding use during the past 20 years of aspirin, prescription and over-the-counter nonselective NSAIDs, and cyclooxygenase-2 (COX-2) inhibitors. A total of 1,000 cases and 1,060 controls contributed data for these interim analyses. Analyses were carried out for men and women and for both sexes combined. After adjustment for age and sex, there was no consistent association between long-term use and NHL for all NSAIDs combined, aspirin, nonselective NSAIDs, and COX-2 inhibitors. For women, long-term aspirin use may be associated with a decreased risk of NHL (for 3

Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy.In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed. From 2010 to 2014, 1494 treated patients were enrolled in the registry by line of therapy (LOT), and stratified by the results of cytogenetic/fluorescence in situ hybridization (FISH) testing into 3 risk levels: unfavorable (presence of del[17p] or del[11q]), favorable (absence of del[17p] and del[11q]), and unknown.Cytogenetic/FISH testing was performed in 861 patients (58%) at enrollment; only 40% of these patients were retested before starting a subsequent LOT. Of those enrolled at the first LOT, unfavorable-risk patients had inferior event-free survival compared with favorable-risk patients (hazard ratio, 1.60; P = .001). Event-free survival was inferior with bendamustine-containing regimens (P .0001). Event-free survival did not differ significantly between risk groups for patients treated with ibrutinib or idelalisib in the relapse/refractory setting. The predictors of reduced event-free survival included unfavorable-risk genetics, age ≥ 75 years, race, and treatment choice at enrollment.The present study has shown that prognostic cytogenetic/FISH testing is infrequently performed and that patients with unfavorable-risk genetics treated with immunochemotherapy combinations have worse outcomes. This underscores the importance of performing prognostic genetic testing for all CLL patients to guide treatment.

8023 Background: t(11;14) is a common cytogenetic abnormality historically associated with standard-risk and generally favorable MM outcomes, but has shown poor prognosis in some retrospective analyses. Connect MM is a prospective, US, observational, multicenter registry that collects data on management and natural history of NDMM pts in clinical practice. The impact of t(11;14) on survival outcomes was assessed in AA and NAA pts. Methods: Adult NDMM pts who completed induction and were tested for t(11;14) by FISH/cytogenetics were grouped by race (AA vs NAA). Endpoints were PFS and OS. Kaplan-Meier analyses were adjusted for differences in cohort, age, ISS stage, transplant intent, t(4;14), hemoglobin, platelets, calcium, creatinine, and diabetes history. Data cutoff was Jul 7, 2016. Results: 3011 pts were enrolled in 2 cohorts (Cohort 1: n = 1493, Sep 2009–Dec 2011, median follow-up = 39.3 mos; Cohort 2: n = 1518, Dec 2012–Apr 2016, median follow-up = 16.4 mos). Of 1539 (52%) pts tested for t(11;14), 363 (24%) were t(11;14)-positive, including 53 (26%) of 205 AA and 310 (23%) of 1334 NAA pts. First-line bortezomib exposure was similar across groups. A trend of shorter PFS was observed in AA pts with t(11;14) vs AA without t(11;14) (Table). AA pts with t(11;14) had significantly higher risk of death compared to those without t(11;14) and higher rate of early mortality than NAA pts. No differences in PFS or OS were noted in NAA pts with or without t(11;14). For OS, the interaction between race and t(11;14) status was statistically significant ( P= 0.004). Conclusions: In Connect MM, the effect of t(11;14) on OS was significantly different between AA and NAA pts. t(11;14) was associated with poorer survival outcomes in AA pts, and thus, may be a risk factor for poor prognosis. Additional analyses will be conducted to elucidate the role of induction treatment, transplant and maintenance in AA and non-AA pts with t(11;14). Clinical trial information: NCT01081028. [Table: see text]

Introduction: Pre-treatment characteristics of pts with CLL, such as del(17p), are used to identify high-risk populations for enrollment onto clinical trials. Nevertheless, little is known about how to identify high-risk pts who are not captured by conventional prognostic tools, yet may benefit from clinical trials. Studies have shown that first-line chemoimmunotherapy (CIT) provides a therapeutic challenge to CLL and confers a selective pressure favorable to the growth of aggressive clones (Landau et al. Nature 2015;526:525-30). Early progression of disease (POD) may reflect specific aspects of disease biology and serve as a post-treatment prognostic marker that defines high-risk pts. Here we describe the characteristics and survival of pts experiencing early POD within 2 years of treatment initiation. Methods: The Connect CLL Registry (NCT01081015), a multicenter, prospective observational cohort study, enrolled 1,494 CLL pts between 2010-2014 from 179 community, 17 academic, and 3 government sites in the USA. Pts were ≥ 18 years and were enrolled ≤ 2 months of initiating any line of therapy (LOT). Of 889 pts who received first LOT (LOT1), 154 were excluded due to subsequent treatment or death without recorded progression. Pts were stratified by early POD (progression with or without transformation ≤ 2 years of treatment initiation), or late/no POD. A 2-year cutoff was found to approximate median time to POD. Cox regression models were used to identify independent predictors of progression or death. Progression-free survival probabilities were estimated by the Kaplan-Meier method and compared between subgroups using the log-rank test. Results: A total of 735 pts with CLL were included in the analysis. Median age was 67 years (range 22-99), 64% were male, 29% had advanced Rai stage (III/IV), and 14% of those with available FISH data had del(17p). At a median follow-up of 42.5 months, 298 (40.5%) pts had POD. Median time to POD was 20 months. A total of 179 (24.3%) pts experienced early POD (≤ 2 years); the remaining 556 pts experienced late POD (> 2 years; 119 [16.2%]) or no POD (437 [59.4%]). Early and late/no POD subgroups showed similar distribution of sex, race, Rai stage, and Charlson comorbidity index (all P > 0.05). The early POD group had a higher median age (70 vs 67 years; P = 0.025), and more frequently had del(17p) (20 [20%] vs 22 [7%], among pts with available FISH; P = 0.001) than the late/no POD group. Comparison of first-line treatment patterns showed pts with early POD were more likely to receive monotherapy and less likely to receive combination CIT compared to pts in the late/no POD group. The most commonly used monotherapy was rituximab (15.1% in early POD vs 11.8% in late POD vs 9.2% in no POD), followed by chlorambucil, bendamustine, fludarabine, and cyclophosphamide. Overall response rates were lower in the early POD group (54% vs 83%; P < 0.001). The 2 subgroups had similar rates of combination CIT and monotherapy use as subsequent treatment following POD. Of 11 pre-, intra- and post-treatment factors associated with survival in univariate analysis (P < 0.1), 3 were independent predictors in a multivariable analysis: early POD, age ≥ 75 years, and high comorbidity index. Notably, treatment duration ≤ 4 months and del(17p) were associated with survival in univariate models but were not independent predictors in a multivariable model. Multivariable analysis revealed pts experiencing early POD had a significantly higher risk of death than those who did not experience early POD (HR 23.0, 95% CI 12.9-40.8; P < 0.0001; Table). Three-year survival was 72% vs 97% (P < 0.0001; Figure) for early POD vs late/no POD. To exclude initial therapy as a possible confounding factor for survival, analyses were repeated on those pts in LOT1 receiving fludarabine, cyclophosphamide, and rituximab (FCR, n = 197) and bendamustine plus rituximab (BR, n = 161), the most common CIT regimens. For pts receiving FCR, the early POD group had inferior survival (HR 47.5, 95% CI 12.3-183.6; P < 0.0001). Similar results were observed in pts treated with frontline BR (HR 60.5, 95% CI 13.2-277.6; P < 0.0001). Conclusion: Disease progression ≤ 2 years after initiation of frontline therapy is an independent negative predictor of survival in pts with CLL. This trend is observed across different treatment regimens. This clinical risk factor identifies a subgroup of high-risk pts who should be considered for enrollment onto clinical trials. Disclosures Farber: Seattle Genetics: Research Funding. Davids:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie, Janssen, Gilead: Consultancy; Celgene Corporation: Consultancy. Grinblatt:Celgene Corporation: Consultancy, Speakers Bureau. Lamanna:Gilead: Research Funding; AbbVie: Research Funding; Genentech: Research Funding; Infinity: Research Funding; Pronai: Research Funding; Celgene Corporation: Research Funding. Mato:Abbvie, Acerta Pharma, Gilead Sciences, ProNAi, TG Therapeutics, Theradex: Research Funding; Abbvie, Gilead Sciences, Pharmacyclics, TG Therapeutics: Consultancy. Nabhan:Celgene, Genentech, Abbvie, Infinity, Cardinal Health: Consultancy; Celgene, Genentech, Seattle Genetics, Astellas: Research Funding. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Flick:Celgene Corporation: Employment, Equity Ownership. Bhushan:Celgene Corporation: Employment, Equity Ownership. Sullivan:Celgene Corporation: Employment, Equity Ownership. Sharman:Seattle Genetics: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; TG Therapeutics: Research Funding. Flowers:Gilead: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Spectrum, Janssen, Infinity, AbbVie, Acerta, Pharmacyclics, TG Therapeutics: Research Funding; Optum Rx, Seattle Genetics, Genentech/Roche: Consultancy; Celgene Corporation: Consultancy, Honoraria.

Introduction: Rituximab (R) improves survival in CLL when added to intensive chemotherapy (such as fludarabine and cyclophosphamide [FCR]), and has been shown to improve progression-free survival when given as maintenance therapy following first- or second-line chemoimmunotherapy. However, early phase 2 studies demonstrated only modest activity of R monotherapy (R mono), particularly at standard dose, and its use as a single agent for pts with CLL has remained controversial. Here we describe the characteristics and outcomes of pts with CLL receiving R mono in a real-world setting. Methods: The Connect CLL registry (NCT01081015), a multicenter, prospective observational cohort study, enrolled 1,494 pts with CLL between 2010-2014 from 179 community, 17 academic, and 3 government sites throughout the USA. Pts were ≥ 18 years and were enrolled ≤ 2 months after initiating any line of therapy (LOT). Pts were treated according to individual physician/patient decision making, and adherence to IWCLL standards cannot be determined. Bone marrow biopsy and CT scans were at the physician's discretion; responses were physician assessed and not centrally reviewed. For this analysis, pts were stratified by first (LOT1) or subsequent LOT (LOT≥2), and by treatment with R mono or other treatments (Tx). Kaplan-Meier methods were used to estimate event-free survival (EFS; event defined as death, progression/relapse, or transformation). A log-rank test was used to evaluate differences in EFS. A multivariate analysis of EFS in LOT1 pts was performed using the Cox regression model. Results: Of the pts enrolled, 105 (11.8%) pts in LOT1 and 81 (13.4%) pts in LOT≥2 received R mono. Of the pts receiving other Tx, 620/784 pts (79%) in LOT1 and 333/524 pts (64%) in LOT≥2 received R in combination. In LOT1, pts receiving R mono were older than pts receiving other Tx (74 vs 67 years; P < 0.0001); in LOT≥2 median ages were comparable (71 vs 70 years). Pts receiving R mono were more likely to have Rai stage 0-1 CLL than pts receiving other Tx, both in LOT1 (63.9% vs 51.8%; P = 0.05) and LOT≥2 (70.4% vs 49.9%; P = 0.005). The proportion of pts receiving R mono vs other Tx with a CCI score of ≥ 4 was similar in LOT1 (25.7% vs 22.8%) and LOT≥2 (32.1% vs 28.4%). Median absolute lymphocyte count at enrollment was lower in pts on R mono vs other Tx in LOT1 (27.7 vs 46.1 x 109/L) but similar in LOT≥2 (35.6 vs 30.2 x 109/L). A lower proportion of pts receiving R mono had FISH/cytogenetics performed at enrollment than pts receiving other Tx in LOT1 (48.6% vs 67.0%; P = 0.0002) and LOT≥2 (30.9% vs 49.6%; P = 0.002). The most common Tx regimens in LOT1 were FCR (25.9%), bendamustine plus R ([BR] 21.0%), R mono (11.8%), fludarabine plus R ([FR] 6.3%), and chlorambucil (4.6%); and in LOT≥2, BR (27.6%), R mono (13.4%), FCR (8.6%), bendamustine (7.4%), FR (4.1%), and ofatumumab (4.0%). The most common reason to initiate treatment in any LOT was bone marrow failure (LOT1, 44.8% vs 39.3%; LOT≥2, 37.0% vs 31.5%; R mono vs other Tx). Duration of therapy was shorter for pts receiving R mono vs other Tx in LOT1 (1.4 vs 4.1 months) and LOT≥2 (1.6 vs 3.3 months). In LOT1, responses were lower in pts on R mono vs other Tx: overall response rate (ORR) was 38.1% vs 64.2% (complete response [CR], 16.2% vs 41.2%; P < 0.0001). In LOT≥2, ORR was 25.9% vs 24.6% for pts on R mono vs other Tx (CR, 9.9% vs 11.5%; P = 0.68). Partial response did not differ significantly between pts receiving R mono vs other Tx in LOT1 and LOT≥2. Pts receiving R mono in LOT1 had inferior median EFS vs other Tx (34 vs 50 months; log-rank P = 0.04); however, after adjusting for factors such as ECOG status and del(17p) status, there was no difference in EFS (HR 0.932; P = 0.79). In pts in LOT≥2, median EFS was similar for R mono and other Tx (15 months for both groups; P = 0.93). Conclusions: Pts receiving R mono as frontline CLL therapy were older than pts receiving other Tx. They also had lower stage disease and lower lymphocyte counts, a shorter duration of treatment, and inferior response rates. Pts receiving R mono in relapsed CLL, more closely approximated pts receiving other Tx in terms of age. Despite the shorter duration of therapy for pts receiving R mono in LOT1 and LOT≥2, both groups had similar ORR and EFS in LOT≥2. These data reinforce the idea that R mono is inadequate as frontline therapy in progressive CLL, and demonstrate the opportunity for improvement in relapsed/refractory disease with novel agents relative to traditional chemoimmunotherapy approaches. Disclosures Sharman: Celgene: Research Funding; Gilead: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; TG Therapeutics: Research Funding; Seattle Genetics: Research Funding. Davids:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie, Janssen, Gilead: Consultancy; Celgene Corporation: Consultancy. Farber:Seattle Genetics: Research Funding. Grinblatt:Celgene Corporation: Consultancy, Speakers Bureau. Lamanna:Gilead: Research Funding; AbbVie: Research Funding; Genentech: Research Funding; Infinity: Research Funding; Pronai: Research Funding; Celgene Corporation: Research Funding. Mato:TG Therapeutics: Consultancy; Abbvie: Research Funding; Acerta Pharma: Research Funding; Gilead Sciences: Research Funding; ProNAi: Research Funding; TG Therapeutics: Research Funding; Theradex: Research Funding; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Abbvie: Consultancy. Nabhan:Astellas: Research Funding; Seattle Genetics: Research Funding; Cardinal Health: Consultancy; Infinity: Consultancy; Abbvie: Consultancy; Genentech: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding. Sullivan:Celgene Corporation: Employment, Equity Ownership. Flick:Celgene Corporation: Employment, Equity Ownership. Kiselev:Celgene Corporation: Employment, Equity Ownership. Bhushan:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Flowers:Seattle Genetics: Research Funding; Optum Rx, Seattle Genetics, Genentech/Roche: Consultancy; Celgene Corporation: Consultancy, Honoraria; Spectrum, Janssen, Infinity, AbbVie, Acerta, Pharmacyclics, TG Therapeutics: Research Funding; Millennium: Consultancy, Research Funding; Gilead: Consultancy, Research Funding.

Background: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer. Objective: To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization. Methods: We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45–69 years who enrolled in the California Men’s Health Study in 2002–3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders. Results: During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of ≥5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers. Conclusion: These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for ≥5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.

Statins have known anticarcinogenic effects, however, evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent. We examined the association between statin use and risk of prostate cancer among 69,047 eligible participants in the California Men's Health Study, a prospective cohort of Northern and Southern California Kaiser Permanente (KP) members, ages 45 to 69 years, initiated in 2002. Prostate cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and since 1994 in Northern California), was treated as time-varying and defined as the cumulative days dispensed of any statin from the first dispensing until a prostate cancer diagnosis, radical prostatectomy, termination of membership, or end of study (December 31, 2004). Cox proportional hazards models with age as the time scale were used to estimate rate ratios, while controlling for confounding variables. During follow-up, 888 prostate cancer cases, including 131 advanced cases, were identified. There was no association between ever statin use or

Purpose Determine the risk of cancer in statin users. Methods Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program's pharmacy records and cancer registry from August 1994 to December 2003. Results Most of the 361,859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2-year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits. Conclusions Overall this study provided no strong evidence of either causation or prevention of cancer by statins.

We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence.The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI).The mean duration of statin use in the cohort among those who initiated use post-diagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39-1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02).Our findings provide initial support for an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence.

The majority of pts with newly diagnosed CLL are classified with Rai stage 0 or 1 disease and typically experience an indolent clinical course. However, little is known regarding the reasons for initiating therapy in this population or patterns of initial treatment in the contemporary era of our practicing community. We utilized data from the Connect CLL registry, a US-based multi-center, prospective observational cohort study that is aimed at understanding patterns of CLL management without a study-specific intervention. Eligible pts were adults with a clinical diagnosis of CLL who initiated therapy ≤2 months prior to enrollment, and were enrolled from academic (n=155), community (n=1311), or government (n=28) sites between 2010-2014. Descriptive statistics were applied to examine data on demographics, baseline characteristics, treatment selection, early treatment outcomes, and reasons for initiating therapy that were reported for pts with Rai 0/1 CLL receiving first-line therapy. Multivariable logistic regression models were constructed to evaluate predictors of complete response (CR) and event-free survival (EFS) defined as the occurrence of the first of disease progression, relapse or death within 24 months of enrollment. Among 684 pts who received first-line therapy at enrollment and for whom Rai stage was available, 363 had Rai 0/1 CLL. This group had a median age of 68 years (range 41-90); 94% were white, 60% male, 98% insured, and 93% were treated in community practices; 47% had Rai stage 0 disease (54% Binet A); 33% had ≥1 constitutional symptoms; 96% had ECOG performance status of 0 or 1; 35% had conventional cytogenetics and 53% had FISH analysis performed. Among pts for whom cytogenetic or FISH analysis were performed, 159 (72%) were abnormal, of them 37 pts (23%) had del(11q), 104 pts (65%) had del(13q), 33 pts (21%) had trisomy 12, and 20 pts (13%) had del(17p) by conventional cytogenetics and/or FISH, including 8% with del(17p) by FISH. The median time from diagnosis to initiation of therapy was 2.5 years (range 0-20 years) for Rai 0/1 pts compared with 0.5 years for pts enrolled with Rai stage ≥2 (range 0-32). The most common reasons for initiating therapy (with >1 reason possible) in Rai 0/1 CLL were: bulky or progressive or lymphadenopathy (40%), progressive lymphocytosis (39%), any disease-related symptom (weight loss, fatigue, fever, night sweats; 28%), anemia (20%), and thrombocytopenia (15%); 42% of pts had >1 reason for initiation. The most common first-line regimens used in this cohort were: fludarabine/cyclophosphamide/rituximab (FCR; 29%), bendamustine/rituximab (BR; 20%), and rituximab alone (12%). Of the 317 pts who either responded to treatment during the first 24 months of enrollment or were followed ≥24 months, 143 pts (45%) achieved CR (investigator assessed as per protocol) and 264 (83%) achieved CR or partial response. Female gender (odds ratio [OR] = 2.22), treatment with BR or FCR (OR = 3.41), and time from diagnosis to therapy (OR = 0.92; with each year increase in time from diagnosis to initiation of therapy, relative odds of CR decreases by 8%), were independent predictors of CR. Of the 311 evaluable pts, 82 pts (26%) experienced an EFS event during the 24 months on study, of which 19 (23%) were deaths and 48 (59%) were progressions. Age ≥75 years (OR = 4.46), lymphocytosis as a reason for therapy initiation (OR = 1.89), and male gender (OR = 1.73) were independent predictors of an EFS event within 24 months. The Connect CLL registry represents the largest comprehensive prospective cohort of CLL pts collected from multiple practices across the US. In concordance with other studies, pts with Rai 0/1 initiated therapy approximately 2.5 years following CLL diagnosis and included a cohort of pts with poor prognostic FISH characteristics. Although chemoimmunotherapy was associated with a significantly higher likelihood of CR, progressive lymphocytosis as a reason for initiating therapy (and not any form of treatment) was more likely to predict an early EFS event. Approaches using novel agents or combination therapies aimed towards addressing pts with progressive lymphocytosis should be considered in future studies. Disclosures Flowers: Seattle Genetics: Consultancy; OptumRx: Consultancy; AbbVie: Research Funding; Pharmacyclics: Research Funding; Gilead Sciences: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; Spectrum: Research Funding; Onyx Pharmaceuticals: Research Funding; Spectrum: Research Funding; Acerta: Research Funding; Gilead Sciences: Research Funding; Janssen: Research Funding; Infinity Pharmaceuticals: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Millennium/Takeda: Research Funding; Onyx Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding. Nabhan:Celgene Corporation: Honoraria, Research Funding. Kay:Pharmacyclics: Research Funding; Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolero Pharma: Research Funding. Mato:AbbVie: Consultancy, Research Funding; Janssen: Consultancy; Celgene Corporation: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Genentech: Consultancy. Lamanna:Genentech-Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Grinblatt:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau. Kipps:Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor; Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor. Kozloff:Roche: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; AbbVie: Consultancy. Sullivan:Celgene Corporation: Employment, Equity Ownership. Flick:Celgene Corporation: Employment, Equity Ownership. Kiselev:Celgene Corporation: Consultancy. Bhushan:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene Corporation: Employment, Equity Ownership. Sharman:TG Therapeutics, Inc.: Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Calistoga: Honoraria; Celgene Corporation: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Roche: Research Funding.

Introduction: Results of several large clinical trials have demonstrated inferior outcomes when CLL patients (pts) with del(17p), or to a lesser extent del(11q), are treated with chemoimmunotherapy. Despite recent advances in targeted therapies, management of unfavorable-risk CLL pts remains challenging. The Connect CLL registry is the largest prospective study describing real-world management of a diverse cohort of CLL pts. Here we describe the management of genetically unfavorable-risk CLL pts enrolled in the Connect CLL Registry, and test associations between del(17p)/del(11q) mutations and treatment choice, timing of therapy, and outcomes. Methods: Connect CLL is a longitudinal, multicenter, observational cohort study of 1,494 CLL pts enrolled between 2010-2014 at 179 community (n=1,311), 17 academic (n=155), and 3 government (n=28) sites within ≤ 2 months of initiating any line of therapy (LOT). For this study, pts were categorized into 3 risk-groups based on FISH or cytogenetic results at enrollment: unfavorable risk [either del(17p)/del(11q) positive]; favorable risk [absence of del(17p)/del(11q)]; and unknown risk (testing not performed). Analyses were stratified by LOT at enrollment (LOT1 vs LOT≥2). The risk of an EFS defining event was compared across risk-groups stratified by LOT, including only pts who had been followed for ≥ 2 years (yr) or those who had an EFS defining event (death, progression/relapse, transformation) within 2 yr, using multivariable (MV) logistic regression. Logistic regression analyses of 18 potential predictors were performed, and significant predictors (0.10 significance level) were then included in a MV logistic regression model to identify factors associated with inferior 2 yr EFS. Results: Of 1,494 pts enrolled, 225 had unfavorable risk [del(17p), n = 94; del(11q), n = 131], 621 favorable risk, and 648 unknown risk. For pts enrolled at LOT1 (n = 889), 141 had unfavorable risk, 425 favorable risk, and 323 unknown risk. Baseline characteristics for unfavorable-risk pts in LOT1 included: median age 69 yr (62% age ≥ 65 yr); 91% White; 53% Rai stage ≥ 2; 86% community sites; 0.9 yr median time from dx to LOT1; 8% family history CLL. With the exception of age, unfavorable-risk pts treated at LOT1 with FCR (median age 63) and BR (median age 74) had similar demographic characteristics. Median time from dx to LOT1 was 1.0, 1.3, and 2.0 yr for unfavorable risk, favorable, and unknown-risk pts, respectively (P < 0.001 for comparison of the 3 risk-subgroups). Reasons for initiating treatment in unfavorable-risk pts were lymphadenopathy (42%), bone marrow failure (36%), and lymphocytosis (33%) (similar across the 3 risk-subgroups). The three most common therapies for unfavorable-risk pts in LOT1 were FCR (36%), BR (21%), and FR (6%). Favorable-risk (FCR 26%, BR 24%, and R 10%) and unknown-risk pts (FCR 22%, BR 18%, and R 17%) were treated similarly in LOT1. Median time from dx to LOT≥2 was 3.5 yr in unfavorable-risk pts (vs 4.1 yr in favorable and 4.6 yr in unknown risk pts; P = 0.04 for comparison of the 3 risk-groups). For unfavorable-risk pts in LOT≥2, BR (26%), R (11%), and FCR (10%) were most commonly prescribed. At any LOT, only 10% of unfavorable-risk pts participated in a clinical trial and 4% underwent allogeneic SCT. Overall, 33% (LOT1) and 68% (LOT≥2) of pts experienced an EFS defining event within 2 yrs. Pts with unfavorable risk (vs favorable risk) had significantly worse outcomes, with a higher-risk of death/progression/relapse/transformation within 2 yr (LOT1: 42% vs 29%, respectively, P = 0.008; and LOT≥2: 80% vs 61%, P = 0.004). Unfavorable-risk pts treated with either FCR or BR at LOT1 had similar risk of an EFS defining event (odds ratio [OR] 0.9, CI 0.6-1.5). Results from MV analyses of LOT1 pts identified unfavorable risk (OR 1.9; 95% CI 1.1-3.1; P = 0.0168) and age ≥ 75 years (OR 2.6; 95% CI 1.5-4.3; P = 0.007) as independent predictors of inferior EFS at 2 yr. Conclusions: Although similar treatment approaches were used among the 3 risk-subgroups, pts with unfavorable-risk CLL had inferior outcomes at LOT1 and LOT≥2. These results, from a real-world setting, validate the findings for unfavorable risk pts from large clinical trials. These data underscore the importance of performing genetic risk stratification on all CLL pts, and support consideration of clinical trials and/or B cell receptor targeted agents for unfavorable risk CLL pts when treatment is considered. Disclosures Mato: Janssen: Consultancy; AbbVie: Consultancy, Research Funding; Genentech: Consultancy; Pronai Pharmaceuticals: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding. Nabhan:Celgene Corporation: Honoraria, Research Funding. Flowers:Celegene: Other: Unpaid consultant, Research Funding; Celegene: Other: Unpaid consultant, Research Funding; Spectrum: Research Funding; Infinity Pharmaceuticals: Research Funding; OptumRx: Consultancy; Onyx Pharmaceuticals: Research Funding; Janssen: Research Funding; AbbVie: Research Funding; Seattle Genetics: Consultancy; Onyx Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Gilead Sciences: Research Funding; Genentech: Research Funding; Acerta: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Millennium/Takeda: Research Funding; Infinity Pharmaceuticals: Research Funding; Spectrum: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics: Research Funding; OptumRx: Consultancy; Gilead Sciences: Research Funding; AbbVie: Research Funding; Seattle Genetics: Consultancy; Acerta: Research Funding. Kay:Pharmacyclics: Research Funding; Genentech: Research Funding; Tolero Pharma: Research Funding; Celgene Corporation: 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; Hospira: Research Funding. Kipps:Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor; Pharmacyclics Abbvie Celgene Genentech Astra Zeneca Gilead Sciences: Other: Advisor. Grinblatt:Celgene Corporation: Consultancy, Honoraria, Speakers Bureau. Lamanna:Genentech-Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kozloff:Genentech: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; AbbVie: Consultancy. Sullivan:Celgene Corporation: Employment, Equity Ownership. Flick:Celgene Corporation: Employment, Equity Ownership. Kiselev:Celgene Corporation: Consultancy. Bhushan:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene Corporation: Employment, Equity Ownership. Sharman:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Calistoga: Honoraria; Roche: Research Funding; TG Therapeutics, Inc.: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Janssen: Research Funding.

Introduction Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non–small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. Methods From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. Results ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2–65.5). Median age was 65 years (range, 31–93), and 252 patients (12.8%) identified as never smokers. Median progression-free survival was 6.6 months (95% confidence interval, 6.3–6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2–13.8) with first-line bevacizumab plus chemotherapy. Incidences of bevacizumab-associated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. Conclusion Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC.