Caplacizumab Frontline Added to Therapeutic Plasma Exchange and Immunosuppression Prevents Unfavorable Outcomes in Immune-Mediated TTP: An International Real-World Study of the TTP-IWG (The Capla 500 Project)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.2636-2636
• Main Authors: Coppo, PAUL, Bubenheim, Michaël, Benhamou, Ygal, Voelker, Linus A., Brinkkoetter, Paul T., Kühne, Lucas, Knoebl, Paul N., Mingot, Maria Eva, Pascual Izquierdo, Maria Cristina, De La Rubia, Javier, Del Rio Garma, Julio, Chaturvedi, Shruti, Masias, Camila, Mazepa, Marshall, Zheng, X. Long, Sinkovits, Gyorgy, Reti, Marienn, Patriquin, Christopher J., Pavenski, Katerina, Boechat, Tiago, Farias, Joao, Ribeiro, Eduardo Flavio Oliveira, de Andrade, Michaela Larissa Lobo, Veyradier, Agnès, Joly, Bérangère, Bouzid, Raïda, Sakai, Kazuya, Matsumoto, Masanori, Mancini, Ilaria, Agosti, Pasquale, Peyvandi, Flora, Stubbs, Matthew James, Hmaid, Amjad, Sharif, Sobia, Dutt, Tina, Cataland, Spero, Lammle, Bernhard, Scully, Marie
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-179316

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) results from autoantibody-mediated severe deficiency of ADAMTS13, the Von Willebrand factor (VWF)-cleaving protease. In this context, ultra-large VWF multimers accumulate in the circulation, leading to increased platelet clumping, with subsequent severe thrombocytopenia, microangiopathic hemolytic anemia and multiorgan failure. The anti-VWF nanobody caplacizumab is licensed for adults with iTTP. Prospective controlled trials and national real-world studies have provided evidence that caplacizumab improved outcome of the acute phase of the disease. However, whether caplacizumab decreases mortality, and the optimal timing of caplacizumab initiation, remain to be determined. To address these questions, an international survey, the Capla 500+ project, has been conducted. An academic call for observations involving experienced teams from 10 worldwide countries recruited 942 adult patients treated with a regimen of daily therapeutic plasma exchange (TPE), caplacizumab and immunosuppression with corticosteroids ± rituximab (caplacizumab group). Cases were compared to historic controls (control group) randomly selected from 2015 to 2018 by 4 teams in a 2:1 ratio (N=495), treated with TPE and immunosuppression. Primary outcome was 3-month survival post-first TPE. Key secondary outcomes were refractoriness and exacerbations, time to clinical response, number of TPE to achieve clinical response, time to ADAMTS13 activity recovery ≥20%, and caplacizumab-related adverse events. Clinical presentation and severity were comparable between groups ( Table). All patients received TPE in both caplacizumab and control groups, in association with corticosteroids (99% and 93%, respectively), and rituximab (92% and 71%, respectively) frontline or as salvage therapy. Caplacizumab was started within 3 days (715 patients), or delayed by≥4 days from first TPE (218 patients); for those with delayed initiation, caplacizumab was added for management of exacerbation or refractoriness (63 cases) or a slow improvement to TPE/immunosuppression (155 cases). The 3-month survival post-first TPE in the caplacizumab group was 98.6% vs 93.3% in the control group (p