title: A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia.
abstract: Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI-WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression-free survival (PFS) of ofatumumab as front-line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI-WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24-month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high-risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well-tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020-1025, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, Nashville, Tennessee.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.affiliation: Division of Hematology and Comprehensive Cancer Center at the Ohio State University, Columbus, Ohio.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Florida Cancer Specialists, Ft. Myers, Florida.
authors.forename: William
authors.initials: W
authors.lastname: Harwin
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Oncology Hematology Care, Cincinnati, Ohio.
authors.forename: David
authors.initials: D
authors.lastname: Waterhouse
authors.affiliation: Hematology-Oncology Associates of Northern NJ, Morristown, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Papish
authors.affiliation: Division of Hematology and Comprehensive Cancer Center at the Ohio State University, Columbus, Ohio.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee.|Tennessee Oncology, Nashville, Tennessee.
authors.forename: John
authors.initials: J
authors.lastname: Hainsworth
authors.affiliation: Division of Hematology and Comprehensive Cancer Center at the Ohio State University, Columbus, Ohio. john.byrd@osumc.edu.|Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio. john.byrd@osumc.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D003582:Cytogenetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D012074:Remission Induction
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C527517:ofatumumab