title: Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.
abstract: Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).
authors.affiliation: Willamette Valley Cancer Institute, Springfield, OR, USA.|US Oncology Research, Morristown, NJ, USA.
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Sharman
authors.affiliation: Carol G. Simon Cancer Center, Morristown, NJ, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Farber
authors.affiliation: West Cancer Center/University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.affiliation: Clearview Cancer Institute, Huntsville, AL, USA.
authors.forename: Marshall T
authors.initials: MT
authors.lastname: Schreeder
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Blue Ridge Cancer Care, Blacksburg, VA, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Brooks
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Compass Oncology, Vancouver, WA, USA.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Kolibaba
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Greenville Health System Cancer Institute, Greenville, SC, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Fanning
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Illinois Cancer Specialists, Niles, IL, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Klein
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Cancer Center of Santa Barbara, Santa Barbara, CA, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Greenwald
authors.affiliation: TG Therapeutics, Inc., New York, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Sportelli
authors.affiliation: TG Therapeutics, Inc., New York, NY, USA.
authors.forename: Hari P
authors.initials: HP
authors.lastname: Miskin
authors.affiliation: TG Therapeutics, Inc., New York, NY, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Weiss
authors.affiliation: US Oncology Research, Morristown, NJ, USA.|Rocky Mountain Cancer Centers, Aurora, CO, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Burke
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018951:Antigens, CD20 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D015202:Protein Engineering; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine; C000619007:ublituximab
keywords: 17-p deletion; chronic lymphocytic leukaemia; high-risk; ibrutinib; ublituximab