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Combination ublituximab and ibrutinib in R/R CLL patients; safe and effective?

Feb 9, 2017

In the February 2017 issue of the British Journal of Haematology, Jeff P. Sharman, from the Willamette Valley Cancer Institute, Springfield, OR, USA, and colleagues reported the results of a phase II study into the efficacy and safety in treating R/R CLL patients with the combination of ibrutinib and the novel anti-CD20 antibody ublituximab (TG-1101). This multicenter study recruited 45 patients, of which 41 were evaluable for efficacy. A six patient dose-confirmation safety cohort was used to define the dosing of ublituximab in combination with ibrutinib. The primary outcome of the study was the ORR (CR+PR), by iwCLL 2008 criteria, of patients and as measured by CT scans at the beginning of Cycle 3 and Cycle 6.

Key Highlights:

  • Treatment:
    • 420mg ibrutinib daily throughout all 6 cycles
    • Six ublituximab IV infusion cycles: Cycle 1: D1–2 = up to 150mg D1, remainder of 900mg dose on D2, D8, D15 = 900mg, then D1 of Cycles 2–6
  • ‘High-risk’ classification in 47% pts who had del11q, del17p, and/or TP53 mutation
  • Anti-CD20 refractory pts = 29%
  • Efficacy:
    • All 41 evaluable pts had a response
    • Two-month ORR = 83%
    • Six-month ORR = 88% (CR = 5%, PR = 83%)
    • ‘High-risk’ pts ORR = 95%, 15% were MRD-negative at six-months by peripheral blood analysis
    • Reduction in nodal size observed in 93% pts by six-months
  • Safety:
    • Most common AEs (>30%) were Infusion-Related Reaction (IRR) (53%), diarrhea (40%), and fatigue (33%)
    • Grade 3/4 AEs (>5%): anemia (11%), neutropenia (11%), thrombocytopenia (7%), and IRR (7%)
    • IRR-based dose-interruptions in 47% pts
    • Four patients discontinued due to AEs: 1 due to diarrhea and 3 unrelated to treatment

In conclusion, the authors state that ibrutinib + ublituximab in R/R CLL patients was shown to result in “rapid and high response rates”. A limitation of this study was the lack of long-term PFS and OS reporting, however an ongoing phase III trial will aim to provide this data in high-risk CLL patients.


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).

  1. Sharman J.P. et al. 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. British Journal of Haematology. 2017 Feb. DOI: 1111/bjh.14447. [Epub ahead of print 2016 Dec 16]