title: Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.
abstract: 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.
  
  
  
  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.
  
  
  
  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 < 0.0001) and chemotherapy-alone regimens (p < 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment < 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006).
  
  
  
  CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients.
  
  
  
  The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010.
authors.affiliation: Cardinal Health Specialty Solutions, Waukegan, IL, 60085, USA. chadi.nabhan@cardinalhealth.com.
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.affiliation: Center for CLL, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mato
authors.affiliation: Emory University, Atlanta, GA, 30322, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.affiliation: NorthShore University HealthSystem, Evanston, IL, 60201, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Grinblatt
authors.affiliation: Leukemia Service, Hematologic Malignancies Section, Division of Hematology/Oncology, New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY, 10032, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lamanna
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, 19107, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Weiss
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Davids
authors.affiliation: Celgene Corporation, Summit, NJ, 07901, USA.
authors.forename: Arlene S
authors.initials: AS
authors.lastname: Swern
authors.affiliation: Celgene Corporation, Summit, NJ, 07901, USA.
authors.forename: Shriya
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Celgene Corporation, Overland Park, KS, 66210, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: Celgene Corporation, San Francisco, CA, USA.
authors.forename: E Dawn
authors.initials: ED
authors.lastname: Flick
authors.affiliation: Celgene Corporation, Summit, NJ, 07901, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kiselev
authors.affiliation: Willamette Valley Cancer Institute and Research Center, Springfield, OR, USA.
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Sharman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage*; D014481:United States; D014740:Vidarabine / Q000008:administration & dosage*
chemical_list: D000069283:Rituximab; D014740:Vidarabine
keywords: Chemoimmunotherapy; Chronic lymphocytic leukemia; Connect® CLL registry; Elderly; Prognostic