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843 Outcomes of Patients with Worsening Acquired Thrombotic Thrombocytopenic Purpura Despite Daily Therapeutic Plasma Exchange in the Phase 3 Hercules Trial

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Poster I
Hematology Disease Topics & Pathways:
Diseases, Bleeding and Clotting, platelets, Biological Processes, Cell Lineage, Thrombotic Disorders, immune mechanism
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Marie Scully, MD1, Javier de la Rubia2,3*, Flora Peyvandi4,5, Spero Cataland6, Paul Coppo7*, Johanna A Kremer Hovinga Strebel8*, Paul Knoebl9*, Katerina Pavenski, MD10*, Filip Callewaert11*, Jessica Minkue Mi Edou12* and Rui de Passos Sousa13*

1Department of Haematology, University College London Hospitals, Cardiometabolic Program, National Institute for Health Research UCLH/UCL Biomedical Research Centre, London, United Kingdom
2Hematology Department, Internal Medicine, School of Medicine and Dentistry, Catholic University of Valencia, Valencia, Spain
3Hospital Doctor Peset, Valencia, Spain
4Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
5Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
6Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
7Department of Hematology, Reference Center for Thrombotic Microangiopathies (CNR-MAT), Saint-Antoine University Hospital, AP-HP, Paris, France
8Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
9Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Wien, Austria
10Departments of Medicine and Laboratory Medicine, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada
11Sanofi, Diegem, Belgium
12Sanofi, Zwijnaarde, Belgium
13Sanofi, Lisbon, Portugal

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening thrombotic microangiopathy. While daily therapeutic plasma exchange (TPE) is the mainstay of therapy, some patients are refractory to treatment and acute mortality remains 10%–20% despite treatment (Scully et al. Br J Haematol. 2012). In the Phase 3 HERCULES trial, 3 placebo-treated patients met the definition of refractoriness versus none in the caplacizumab group (Scully et al. N Engl J Med. 2019). There was a subgroup of patients with a complicated disease course despite daily TPE, without meeting the definition of refractoriness. Here, we describe outcomes of patients with suboptimal responses to TPE.

In this post hoc analysis of the HERCULES intent-to-treat population (caplacizumab, n=72; placebo, n=73), we identified patients with a suboptimal response to daily TPE, defined by decreasing platelet counts and increasing lactate dehydrogenase (LDH) after initial but nonsustained partial improvement of platelet count and LDH during daily TPE. Baseline disease characteristics (previous thrombotic thrombocytopenic purpura [TTP] episodes, platelet count, cardiac troponin I, LDH, serum creatinine, disease severity) and treatment outcomes (time to platelet count response, time to stop daily TPE, death, exacerbation) were descriptively summarized.

No patients in the caplacizumab group and 8 (11%) patients in the placebo group demonstrated a suboptimal response to TPE. Baseline disease characteristics were variable (Table 1). Their median time to achieve platelet count response was 10.88 days and median time to stop daily TPE 13.5 days (ranges: see Table 1), compared with 2.88 and 7.00 days, respectively, in the overall HERCULES placebo group. One patient had worsening TTP that led to coma and death. Subsequent exacerbations were reported in 5/8 patients receiving placebo (63%).

These results show the unpredictability of suboptimal responses to TPE, which can be fatal, and which were not observed in the caplacizumab group. This highlights the importance of the fast and sustained protective response observed with caplacizumab treatment in patients with aTTP.

Disclosures: Scully: Takeda: Consultancy, Speakers Bureau; Novartis: Other: Advisory Board, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Ablynx/Sanofi: Consultancy, Other: Advisory Board, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Shire/Takeda: Other: Advisory Board, Research Funding, Speakers Bureau; Takeda: Speakers Bureau. de la Rubia: Janssen: Consultancy, Other: Expert Testimony; Celgene: Consultancy, Other: Expert Testimony; Amgen: Consultancy, Other: Expert Testimony; Ablynx/Sanofi: Consultancy, Other: Expert Testimony. Peyvandi: Octapharma: Research Funding. Cataland: Ablynx/Sanofi: Consultancy, Research Funding; Alexion: Consultancy, Research Funding. Coppo: Shire/Takeda: Other: Advisory Board, Speakers Bureau; Ablynx, a Sanofi company: Other: Advisory Board, Speakers Bureau; Alexion: Other: Advisory Board, Speakers Bureau. Kremer Hovinga Strebel: Siemens: Speakers Bureau; Roche: Speakers Bureau; CSL Behring: Speakers Bureau; Shire/Takeda: Other: Advisory Board, Research Funding; Ablynx/Sanofi: Other: Advisory Board, Speakers Bureau; Ablynx/Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: advisory board, Speakers Bureau; SHIRE/TAKEDA: Membership on an entity's Board of Directors or advisory committees, Other: advisory board, Research Funding. Knoebl: Ablynx/Sanofi: Other: Advisory Board, Speakers Bureau; Shire/Takeda: Other: Advisory Board, Speakers Bureau; CSL Behring: Other: Advisory Board, Speakers Bureau; Roche: Other: Advisory Board, Speakers Bureau; Novo Nordisk: Other: Advisory Board, Research Funding, Speakers Bureau. Pavenski: Bioverativ: Research Funding; Shire/Takeda: Honoraria; Octapharma: Research Funding; Alexion: Honoraria, Research Funding; Sanofi: Research Funding; Ablynx/Sanofi: Honoraria, Research Funding. Callewaert: Sanofi: Current Employment. Minkue Mi Edou: Sanofi: Current Employment. de Passos Sousa: Sanofi: Current Employment.

*signifies non-member of ASH