OC 04.4 - Disease Relapse in immune Thrombotic Thrombocytopenic Purpura and treatment with Anti-CD20 Monoclonal Antibodies – 10-years’ experience from the UK TTP Registry

Saturday, July 9, 2022

1:45 PM – 2:00 PM

Location: ICC Capital Suite Room 14-16

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
Tina Dutt, PhD

Consultant Haematologist
Liverpool University Hospitals NHS Foundation Trust
Liverpool, 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
JV

Joost Vanveen

Consultant Haematologist
Sheffield Teaching Hospitals NHS Trust
Sheffield, England, United Kingdom
JH

Joannes Hermans

Consultant Haematologist
Nottingham University Hospitals NHS Trust
Nottingham, England, United Kingdom
TC

Tanya Cranfield

Consultant Haematologist
Portsmouth Hospitals University NHS Trust
Portsmouth, England, United Kingdom
QH

Quentin Hill

Consultant Haematologist
The Leeds Teaching Hospitals NHS Trust
Leeds, England, United Kingdom
Beverley J. Hunt, MD, FRCP, FRCPath

Professor of Thrombosis & Haemostasis, Consultant Haematologist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom
AC

Amanda Clark

Consultant Haematologist
University Hospitals Bristol NHS Foundation Trust
Bristol, England, United Kingdom
TN

Tim Nokes

Consultant Haematologist
University Hospital Plymouth NHS Trust
Plymouth, England, United Kingdom
SB

Sylvia Benjamin

Consultant Haematologist
Oxford University Hospital NHS Foundation Trust
Oxford, England, United Kingdom
Catherine N. N. Bagot, Dr MBBS MD

MD, PhD
Department of Haematology, Glasgow Royal Infirmary, Glasgow, United Kingdom
Glasgow, Scotland, United Kingdom
NC

Nichola Cooper

Department of Medicine
Hammersmith Hospital
London, England, United Kingdom
SA

Steven Austin

Consultant Haematologist
St George's University Hospital NHS Foundation Trust
London, England, United Kingdom
Mari Thomas, MD, PhD

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

John-Paul Westwood

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: Relapse in immune Thrombotic Thrombocytopenic Purpura (iTTP) is well-characterised with subclinical ADAMTS13 relapses prior to clinical relapses. Rituximab is effective in preventing relapses in patients with iTTP.

Aims: We describe patterns of disease relapse over a 10-year period with a minimum 4-year review and response to anti-CD20 treatments.

Methods: 443 patients were identified between 2008-2018 from 30 sites. Relapse was defined as either clinical relapse, presenting with thrombocytopenia and/or ADAMTS13 relapse, with activity levels < 15%/IU/dL. Clinical details, treatments and responses were reviewed.

Results: 312/443 patients (70.4%) had no relapse following presentation. 131/443 (29.6%) had relapse episodes (45 had clinical relapses only (10%), 56 had ADAMTS13 relapses only (13%) and 30 has both (7%)). Black Caribbeans ethnicity was more common in relapsing patients (16.8% vs 7.1%, p=0.017). 28/443 patients (6.3%) had ‘frequent’ relapses (>0.5 episodes/year) with the remaining (n=103, 23.3%) having ‘infrequent’ relapses (≤0.5 episodes/year).

197 pre-emptive treatment episodes were reported in 89 patients – 181 rituximab (91.9%), 1 obinutuzimab (0.5%), 15 ofatumumab (7.6%). Treatment response (ADAMTS13 activity ≥30%/IU/dL) occurred in 155/167 (92.8%) episodes (91% patients) with complete response (ADAMTS13 activity ≥60%/IU/dL) occurring in 132/167 treatment episodes (79.0%). 8/98 patients (8.2%) were considered minimally responsive to anti-CD20 treatment (ADAMTS13 activity < 30% despite treatment). No patients who initially responded to anti-CD20 therapy subsequently lost response with retreatment. In patients with ‘frequent’ and ‘infrequent’ relapses, there was no difference in ∆ADAMTS13 activity following treatment (86.5% vs 73.2%, p=0.07) nor end-of-treatment absolute CD19-positive lymphocytes (0 vs 0.001x10^9/L, p=0.62).

Conclusion(s): Approximately 30% have a relapsing disease pattern with 6% having frequent relapses requiring treatment ≤ 2-yearly. Anti-CD20 treatment was an efficacious option with a normalisation of ADAMTS13 activity in the majority with persisting responses with further relapses. However, a minority (8%) failed to achieve a significant increase in ADAMTS13 activity following anti-CD20 treatment requiring alternative treatment modalities.