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Objective: To evaluate how treatment regimens in informCLL aligned with NCCN Guidelines®-recommended regimens for CLL/SLL. Patients: Patients receiving approved CLL treatment were categorized by del(17p)/TP53 mutation status, line of therapy, and age/comorbidity. Significant comorbidities (SC) were defined as Charlson Comorbidity Index (CCI) ≥3. Age/comorbidity groups for patients without del(17p)/TP53mut: frail (≥65 years)+SC; elderly (≥65) without SC or younger ( Results: In informCLL (N=1462; previously untreated [1L], 58%; relapsed/refractory [R/R], 42%), community-based practices enrolled 93%. Median age: 71 years (34–95); median CCI: 1.0 (0–11); CCI ≥3: 16%. 27% of patients (n=389) had del(17p)/TP53mut data available. 59%–64% with del(17p)/TP53mut and 68%–100% without del(17p)/TP53mut received NCCN-recommended regimens. For patients with del(17p)/TP53mut, 62% 1L and 44% R/R received recommended category-2A ibrutinib; 24% 1L and 21% R/R had non-recommended CIT (BR/FCR). For patients without del(17p)/TP53mut and frail+SC, 60% 1L had category-1 ibrutinib or obinutuzumab+chlorambucil, but 24% received non-recommended BR; all R/R patients had category-1 ibrutinib or idelalisib+rituximab. For patients without del(17p)/TP53mut and elderly/younger+SC, 69% 1L and 58% R/R patients had category-1 ibrutinib or category-2A BR. For patients without del(17p)/TP53mut and younger without SC, 87% 1L and 82% R/R had BR (category-2A), FCR (1L: category-1; R/R: category-2A), or ibrutinib (1L: category-2A; R/R: category-1). For patients without del(17p)/TP53mut data available (73%, n=1073), ibrutinib (44%), CIT (32%), and anti-CD20 monotherapy (14%) were the most common regimens. Conclusions: Of patients with del(17p)/TP53mut, one-third received non-NCCN-recommended regimens. Given most patients in informCLL lacked del(17p)/TP53mut data and may have received suboptimal therapy, there is a need for awareness of guidelines recommendations to better inform treatment decisions. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.2.2017 - February 21, 2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed 08/08/2017. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Context Understanding clinical characteristics and treatment selection for elderly patients is essential in the era of novel agents. informCLL ( NCT02582879 , September 2015 initiation) is an ongoing, US-based, prospective, real-world observational registry of patients with CLL. Objective To characterize overall demographics of previously untreated elderly CLL patients and compare clinical factors and treatment choice of those aged 65-74 years (Group 1) versus ≥75 years (Group 2). Design/Patients An interim analysis (November 2018 data cut) of previously untreated patients from the informCLL registry who were aged ≥65 years and received single-agent ibrutinib, chemoimmunotherapy, or immunotherapy at enrollment. Association between age groups and treatment choice was assessed by multinomial logistic regression after adjusting for comprehensive demographic and clinical factors. Results Analysis included 449 elderly patients (Group 1: 238; Group 2: 211); median age was 74 years. Most patients were male (64.1%), white (92.4%), treated in community settings (94.9%), and Medicare/Medicaid-insured (88.4%). Median time from initial diagnosis to first treatment was 2.0 years. The majority had an Eastern Cooperative Oncology Group (ECOG) score ≤ 1 (87.1%) and Charlson Comorbidity Index (CCI) score ≤ 1 (62.0%). The most common comorbidities were hypertension (69.3%), other cardiovascular disorders (29.2%), non-CLL malignancies (26.3%), and connective tissue diseases (24.5%). Documented cytogenetic/molecular testing rates were low: TP53, 6.01%; IGHV, 5.35%; CLL FISH, 17.8%; any of the three, 18.7%. 202 (45.0%) patients received ibrutinib, 170 (37.9%) received chemoimmunotherapy, and 77 (17.1%) received immunotherapy. Group 2 (vs Group 1) had poorer performance status (ECOG scores ≥2, 12.9% vs 5.7%, p=0.01), more comorbidities (CCI scores ≥2, 45.5% vs 31.1%, p Conclusions Previously untreated real-world CLL patients aged ≥75 years (vs 65-74 years) had poorer performance status, more comorbidities, lower cytogenetic/molecular testing rates, and a higher likelihood of receiving ibrutinib versus chemoimmunotherapy as initial treatment.

Background: Bruton tyrosine kinase (BTK) is a critical component of B-cell receptor signaling pathway and a validated therapeutic target for CLL. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor with minimal off-target activity that has been shown to have an overall response rate (ORR) of 95% (85% partial response [PR]; 10% PR with lymphocytosis [PRL]) after a median follow-up of 14.3 months in the relapsed CLL cohort of the Phase 1/2 ACE-CL-001 study. We present an updated analysis of the safety and efficacy results from the TN cohort of CLL patients from ACE-CL-001. Methods: Patients with TN CLL/small lymphocytic lymphoma (SLL) were eligible if they met International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for treatment, had an ECOG performance status of ≤2, and declined or were not appropriate candidates for chemotherapy. Patients received oral acalabrutinib 100 mg twice daily (BID) or 200 mg daily (patients were started on 200 mg QD and then switched to 100 mg BID) until progressive disease or unacceptable toxicity. Safety was the primary endpoint. Secondary endpoints were investigator-assessed overall response rate (ORR) by IWCLL 2008 criteria with modification for lymphocytosis, duration of response (DOR) and progression-free survival (PFS). Time to response (TTR; ≥ PR) and event-free survival (EFS) were exploratory endpoints. Results: A total of 99 patients (100 mg BID, n=62; 200 mg QD, n=37) were treated. The median age was 64 years (range 33-85), 46% of patients had bulky lymph nodes ≥5 cm, 47% had Rai stage III-IV disease at baseline, 10% (9/91) of patients had del(17p), and 62% (57/92) of patients had unmutated IGHV. As of December 1, 2017, the median time on study was 33 (1-39) months, with 91% of patients remaining on study treatment. Nine patients discontinued therapy: adverse events (n=5; 5%), pregnancy, disease progression, patient withdrawal, and initiation of subsequent therapy (n=1 each; 1%). The most common AEs (all grades; >20% of patients) were diarrhea (47%), headache (44%), contusion (34%), upper respiratory tract infection (33%), weight increase (30%), arthralgia (29%), nausea (26%), and cough (23%); the majority of these most common AEs were Grade 1/2. Grade 3/4 AEs occurred in 49% (49/99) of patients, most commonly (>2% of patients) neutropenia (7%), diarrhea (5%), headache (5%), nausea (4%), pneumonia (4%), hypertension (3%), and syncope (3%). Atrial fibrillation and hypertension (all grades vs grade 3/4) occurred in 6% vs 1% of patients and 14% vs 3% of patients, respectively. The most common bleeding events (>15%) were contusion (34%), petechiae (18%), and ecchymosis (16%); all bleeding events (60%) were Grade 1/2 except for 2 Grade 3 events (hematuria, upper gastrointestinal hemorrhage). Approximately 34% (34/99) of patients reported serious AEs (all grades), most commonly (≥5 patients) infection (pneumonia [4 patients], influenza [2 patients], and sinusitis [2 patients]). One grade 5 event (multiorgan failure due to neutropenic sepsis/pneumonia) was reported, which was considered unrelated to acalabrutinib. AEs leading to treatment discontinuation (5%) were secondary malignancies (angiosarcoma, glioblastoma multiforme, small cell lung cancer), neutropenic sepsis (Grade 2), rash (Grade 3), and urinary tract infection (Grade 3). ORR was high (97%) for this patient cohort (Table). Median DOR for the 96 responders (≥ PR) and median PFS for the 99 treated patients were not reached (NR) (95% CI: NR, NR; Figure 1). The 36-month DOR and PFS rate was 99% (95% CI: 91%, 100%) and 98% (95% CI: 92%, 100%), respectively. The EFS (with events defined as progression, death, discontinuation due to AE, or start of new anticancer therapy) was estimated to be 94.9% (95% CI: 88.2%, 97.9%) at 24 months (Figure 2). Median TTR was 3.7 months (range 2-22). For the 5 patients who achieved complete response (CR), the median time to CR was 28 months. One CLL progression was reported. No Richter's transformation occurred. Conclusion: Acalabrutinib monotherapy produced high response rates and demonstrated an acceptable safety profile in patients with TN CLL. Disclosures Furman: Gilead: Consultancy; Loxo Oncology: Consultancy; Acerta: Consultancy, Research Funding; Genentech: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy; Incyte: Consultancy, Other: DSMB; Janssen: Consultancy; AbbVie: Consultancy. Martin:Gilead: Consultancy; Janssen: Consultancy; Bayer: Consultancy; Seattle Genetics: Consultancy; AstraZeneca: Consultancy; Kite: Consultancy. O'Brien:Janssen: Consultancy; GlaxoSmithKline: Consultancy; Acerta: Research Funding; Pfizer: Consultancy, Research Funding; Alexion: Consultancy; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy; Sunesis: Consultancy, Research Funding; Celgene: Consultancy; Vaniam Group LLC: Consultancy; Astellas: Consultancy; Abbvie: Consultancy; Aptose Biosciences Inc.: Consultancy; Gilead: Consultancy, Research Funding; Kite Pharma: Research Funding; Regeneron: Research Funding; TG Therapeutics: Consultancy, Research Funding. Brown:Celgene: Consultancy; Verastem: Consultancy, Research Funding; Janssen: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Boehringer: Consultancy; Sun Pharmaceutical Industries: Research Funding; Gilead: Consultancy, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; TG Therapeutics: Consultancy; Roche/Genentech: Consultancy; Invectys: Membership on an entity's Board of Directors or advisory committees; Loxo: Consultancy. Barrientos:Pharmacyclics/Abbive: 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; Janssen: Membership on an entity's Board of Directors or advisory committees. Devereux:Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Other: Personal fees. Hillmen:Novartis: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Alexion Pharmaceuticals, Inc: Consultancy, Honoraria; Acerta: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Research Funding; Gilead Sciences, Inc.: Honoraria, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pagel:Gilead: Consultancy; Pharmacyclics, an AbbVie Company: Consultancy. Chen:Acerta Pharma: Employment. Hamdy:Acerta Pharma: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: various patents for ACP-196. Izumi:Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acerta Pharma, various patents for ACP-196. Patel:Acerta Pharma: Employment, Equity Ownership. Wang:Acerta Pharma: Employment. Jain:Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Pfizer: Research Funding; Abbvie: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Research Funding; Incyte: Research Funding; BMS: Research Funding; ADC Therapeutics: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Infinity: Research Funding; Pfizer: Research Funding; Celgene: Research Funding; ADC Therapeutics: Research Funding; Astra Zeneca: Research Funding; Seattle Genetics: Research Funding; Servier: Research Funding; Verastem: Research Funding; Incyte: Research Funding; Cellectis: Research Funding; Celgene: Research Funding; Adaptive Biotechnologioes: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologioes: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wierda:AbbVie, Inc: Research Funding; Genentech: Research Funding.

302 Second Interim Analysis of a Phase 3 Study Evaluating Idelalisib and Rituximab for Relapsed Chronic Lymphocytic Leukemia John M. Pagel, Steven E. Coutre, Richard R. Furman, Jeff P. Sharman, Bruce D. Cheson, Peter Hillmen, Jacqueline C. Barrientos, Andrew D. Zelenetz, Thomas J. Kipps, Ian W. Flinn, Ghia Paolo, Herbert A. Eradat, Thomas Ervin, Nicole Lamanna, Bertrand Coiffier, Andrew Pettitt, Xiaoming Li, Thomas M. Jahn, Susan M. O’Brien, Michael J. Hallek 1Fred Hutchinson Cancer Research Center, Seattle, United States, 2Stanford Cancer Center, Stanford, 3Weill Cornell Medical College, New York, 4Willamette Valley Cancer Institute and Research Center/US Oncology Research, Springfield, 5Georgetown University Medical Center, Washington, 6The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom, 7Hofstra North Shore-LIJ School of Medicine, Hampstead, 8Memorial Sloan Kettering Cancer Center, New York, 9University of California School of Medicine, San Diego, 10Sarah Cannon Research Institute, Nashville, 11David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, 12Columbia University Medical Center, New York, United States, 13Lyon Sud University Hospital, Pierre-Benite, France, 14University of Liverpool, Liverpool, United Kingdom, 15Gilead Sciences, Foster City, 16Gilead Sciences, Foster City 17University of Texas MD Anderson Cancer Center, Houston, United States, 18University of Cologne, Cologne, Germany Introduction: Idelalisib (IDELA), an oral inhibitor of PI3Kδ, is highly active in heavily pretreated patients with CLL as a single agent or combined with rituximab (R) as demonstrated in Phase 1 trials. Objectives: This report presents the results from the second interim analysis of a Phase 3, randomized, double-blind, placebo-controlled study of IDELA+R vs. placebo (PBO)+R. Methods: Patients with CLL requiring therapy after progression

S24 analysis. Results: Trisomy12 (38-80% of cells) and NOTCH1 mutation (53-100% of cells) was detected in all patients. All patients had two or more cell populations defined by NOTCH1 mutation, Trisomy12 or both (major clone in 2/5 cases). Two patients demonstrated further intra-clonal diversity through either convergent or parallel evolution of two different or identical NOTCH1 mutations in Trisomy12 sub-clones, respectively. Conclusions: Trisomy12-NOTCH1 evolution is more complex than previously thought and may provide insight into progression and transformation. Grant Acknowledgements: Wessex Medical Research Innovation award, Kay Kendal Leukaemia Fund.

304 Ibrutinib Versus Ofatumumab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Results From the Randomized Phase III RESONATETM (PCYC-1112) Trial J Jennifer R. Brown, MD, PhD1, John C. Byrd, MD2, Susan O’Brien, MD3, Jacqueline C. Barrientos, MD4, Neil E. Kay, MD5, Nishitha M. Reddy, MBBS, MD6, Steven Coutre, MD7, Constantine S. Tam, MBBS, MD8, Stephen Mulligan, MBBS, PhD, FRACP, FRCPA9, Ulrich Jaeger, MD10, Stephen Devereux, PhD, FRCP, FRCPath11, Paul M. Barr, MD12, Richard Furman, MD13, Thomas Kipps, MD, PhD14, Florence Cymbalista, MD, PhD15, Maria Fardis, PhD, MBA16, Jesse McGreivy, MD16, Fong Clow, DSc16, Danelle F. James, MD, MAS16, Peter Hillmen, MD, PhD, FRCP, FRCPath17 1Dana-Farber Cancer Institute, Boston, MA, USA; 2The Ohio State University Medical Center, Columbus, OH, USA; 3University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4North Shore Long Island Jewish Health System, Manhasset, NY, USA; 5Mayo Clinic, Rochester, MN, USA; 6Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 7Stanford University School of Medicine, Stanford, CA, USA; 8Peter MacCallum Cancer Centre and St. Vincent’s Hospital, Melbourne, Australia; 9Royal North Shore Hospital, Sydney, Australia; 10Medical University of Vienna, Vienna, Austria; 11Kings College Hospital, NHS Foundation Trust Denmark Hill, London, UK; 12University of Rochester Cancer Center, Rochester, NY, USA; 13Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA; 14Moores UCSD Cancer Center, San Diego, CA, USA; 15Hopital Avicenne, Paris, France; 16Pharmacyclics, Inc., Sunnyvale, CA, USA; 17The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, UK Context: Ibrutinib, a first-in-class, once-daily oral, covalent inhibitor of Bruton’s tyrosine kinase, demonstrated single-agent activity and an acceptable safety profile in a phase II relapsed/refractory (R/R) CLL/SLL study (Byrd et al. NEJM 2013). Ibrutinib is FDA approved for CLL patients who have received ≥1 prior therapy, and for patients with del(17p) CLL. Objective: Interim safety and efficacy results from an international, multicenter, open-label, randomized phase III study of single-agent ibrutinib vs ofatumumab in R/R CLL/SLL Patients: Patients with R/R CLL/SLL who received ≥1 previous therapy considered inappropriate for purine analogs Main Outcome Measures: Independent Review Committee-assessed PFS (primary); overall survival (OS), ORR, safety (secondary) Intervention: 420 mg oral ibrutinib daily or IV ofatumumab 300/2000 mg (12 doses) Results: 391 patients (median age 67 years, 40% ≥70 years, 30% del17p); 195 randomized to ibrutinib, 196 to ofatumumab. Ibrutinib patients had median 3 prior therapies vs 2 for ofatumumab. Ibrutinib significantly improved PFS (median not reached vs 8.1 months; HR 0.215, 95% CI 0.146-0.317, P