title: Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial.
abstract: BACKGROUND
  Although several consolidation strategies to prolong treatment-free survival (TFS) in chronic lymphocytic leukaemia have been investigated, most have proven either ineffective or toxic. Ofatumumab is a human type I anti-CD20 antibody approved by the US Food and Drug Administration as maintenance treatment of patients with recurrent or progressive chronic lymphocytic leukaemia who are in complete or partial response after at least two lines of treatment; higher efficacy might be observed if used as consolidation strategy than without consolidation in previously untreated patients.
  
  
  METHODS
  We recruited patients with previously untreated progressive chronic lymphocytic leukaemia who had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate renal and hepatic function from centres in the USA. Patients with recent myocardial infarction; class III or IV heart failure; uncontrolled, HIV, or active hepatitis B or C infection; or active haemolytic anaemia were excluded. In the first arm of this study, which has been previously reported, patients were treated with six cycles of induction with pentostatin (2 mg/m(2) on day 1), cyclophosphamide (600 mg/m(2) on day 1), and ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg/m(2) on day 2; cycles 2-6: 1000 mg/m(2) on day 1) given intravenously every 21 days. Here were report the second arm, where patients received the same regimen as the first arm, with the addition of six cycles of consolidation with ofatumumab (1000 mg once every 4 weeks), also given intravenously. The primary endpoint was TFS at 18 months, assessed in those who began consolidation. We estimated the distribution of TFS using the Kaplan-Meier method, assessing between-group differences with log-rank statistics. The phase 2 trial, which is completed, is registered at ClinicalTrials.gov, number NCT01024010.
  
  
  RESULTS
  Between Sept 21, 2011, and Nov 7, 2012, 34 patients were recruited to this second arm of the trial. Among the 31 (91%) patients who completed induction treatment and started consolidation, 26 (84%) completed the planned six cycles of ofatumumab consolidation. TFS at 18 months was 94·1% (95% CI 78·5-98·5). Grade 3 or worse adverse events deemed at least possibly related to treatment were neutropenia (14 [41%] patients), infection (2 [6%]), and one (3%) each with anaemia, haemolysis, fatigue, and a neurological, metabolic, respiratory, and vascular complication.
  
  
  CONCLUSIONS
  Ofatumumab-based consolidation appears to be a well tolerated and effective consolidation strategy in patients with chronic lymphocytic leukaemia, which could improve survival.
  
  
  BACKGROUND
  GlaxoSmithKline.
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Paolo
authors: P
authors: Strati
authors: Duke University Medical Center, Durham, NC, USA.
authors: Mark
authors: M
authors: Lanasa
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Timothy G
authors: TG
authors: Call
authors: Mayo Clinic College of Medicine, Scottsdale, AZ, USA.
authors: Jose F
authors: JF
authors: Leis
authors: Duke University Medical Center, Durham, NC, USA.
authors: Danielle M
authors: DM
authors: Brander
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Betsy R
authors: BR
authors: LaPlant
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Adam M
authors: AM
authors: Pettinger
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Wei
authors: W
authors: Ding
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Sameer A
authors: SA
authors: Parikh
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Curtis A
authors: CA
authors: Hanson
authors: Mayo Clinic College of Medicine, Jacksonville, FL, USA.
authors: Asher A
authors: AA
authors: Chanan-Khan
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Deborah A
authors: DA
authors: Bowen
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Michael
authors: M
authors: Conte
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: Neil E
authors: NE
authors: Kay
authors: Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: shanafelt.tait@mayo.edu.
authors: Tait D
authors: TD
authors: Shanafelt
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015649:Pentostatin; D003520:Cyclophosphamide; C527517:ofatumumab