PB0297 - The use of Obinutuzumab and Ofatumumab in the treatment of immune Thrombotic Thrombocytopenic Purpura

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Andrew J. Doyle, MBChB MRCP FRCPath

Consultant Haematologist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom

Co-Author(s)

MS

Matthew Stubbs

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom
WL

Will Lester

Consultant Haematologist
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, United Kingdom
WT

Will Thomas, MD

Consultant Haematologist
Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom
JW

John-Paul Westwood

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom
Mari Thomas, MD, PhD

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom
CP

Charles Percy

Consultant Haematologist
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, United Kingdom
Nithya Prasannan

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom
MS

Marie Scully

Professor
Bloomsbury Institute of Intensive Care Medicine
London, England, United Kingdom

Background: Immune Thrombotic Thrombocytopenic Purpura (iTTP) is an autoantibody-driven condition targeting the ADAMTS13 protein. Eradication of B-cell lymphocytes with rituximab has proven to be efficacious in patients with iTTP at disease presentation and relapse. However, a small number of patients are unable to receive rituximab due adverse drug reactions including rituximab-induced serum sickness (RISS)

Aims: We aimed to review cases of patients with iTTP who received the alternative humanised anti-CD20 monoclonal antibodies, ofatumumab and obinutuzumab for treatment response and adverse events.

Methods: Data from the UK TTP Registry was reviewed for clinical details, disease relapse and treatment response of patients with iTTP receving ofatumumab and obinutuzumab.

Results: 15 patients were identified with 26 treatment episodes with either ofatumumab (n = 18) or obinutuzimab (n = 8). 21/26 episodes were pre-emptive treatment in ADAMTS13 relapses, 4/26 episodes were as part of treatment for clinical relapses and 1/26 episode was during the acute presentation period. All patients had previously received rituximab but was clinically felt inappropriate for further treatments - 12/15 had rituximab-induce serum sickness, 1/15 had acute drug intolerance and 2/15 had short duration of response to rituximab. Other immunosuppressive agents had been used in 5/15 with poor / non-sustained responses.

All patients achieved a remission following treatment with ofatumumab or obinutuzimab – 24/26 episodes achieved complete remission (ADAMTS13 activity =/>60%) and 2/26 achieved partial remission (ADAMTS13 activity 30-50%). The median time to complete remission was 15 days (interquartile range 11.5 – 32.5 days). There were 4/26 (15%) episodes of adverse events - two infections and two atopic episodes.

Conclusion(s): Our data shows that ofatumumab or obinutuzimab should be considered as an option in patients with iTTP unable to have rituximab as part of treatment but have previously been responsive.