-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2673 Caplacizumab As New Paradigm-Changing Therapy for Patients with Autoimmune Thrombotic Thrombocytopenic Purpura (aTTP): Real-World Data from TTP Spanish Registry

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Poster III
Hematology Disease Topics & Pathways:
antibodies, Biological, Diseases, Bleeding and Clotting, Therapies, TTP
Monday, December 7, 2020, 7:00 AM-3:30 PM

Irene García García1*, Moraima Jiménez2*, David Valcárcel, MD, PhD3, Maria Eva Mingot-Castellano, PhD, MD4*, Maria Cristina Pascual Izquierdo, PhD, MD5*, Aurora Viejo, MD6*, Miquel Lozano7*, Rosa Goterris, MD8*, Jorge Martínez Nieto9*, Ana Oliva, MD10*, Inés Gómez-Seguí, PhMD11*, Luis Hernandez, MD12*, Saioa Zalba13*, Verónica Campuzano14*, Yolanda Martínez15*, Helena González16*, Inmaculada Tallon17*, Miguel Fernández Zarzoso18*, Gemma Moreno Jiménez, MD19*, Sunil Lakhwani Lakhwani20*, Sandra Ortega21*, María Solé22*, Jon Ander Atucha Fernández23*, Julio Del Rio-Garma, MD24* and Joan Cid, MD, PhD7*

1Hematology and Hemotherapy, Hospital Universitario Ramón y Cajal, Madrid, Spain
2Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain
3Hematology Department, Department of Hematology. Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron., Barcelona, Spain, Barcelona, Spain
4Hospital Universitario Virgen del Rocio, Sevilla, Spain
5Hematology, Hospital Universitario Gregorio Marañon, Madrid, Spain
6Transfusion Medicine, La Paz University Hospital-IdiPAZ, Madrid, Spain
7Hospital Clínic, Barcelona, Spain
8Hospital Clinico Universitario de Valencia, Valencia, Spain
9Hospital Clínico San Carlos, Madrid, Spain
10H Universitario V de la Candelaria, Tenerife, Spain
11Servicio de Hematología. Hospital La Fe, Valencia, Spain, Valencia, Spain
12Hospital General Universitario de Alicante, Alicante, Spain
13Complejo Hospitalario de Navarra, Pamplona, Spain
14Hospital Universitario de Burgos, Burgos, Spain
15Fundación Jiménez Díaz, Madrid, Spain
16Hospital General de Villalba, Villalba, Spain
17Hospital Virgen Macarena, Sevilla, Spain
18Hospital Universitario Dr. Peser, Valencia, Spain
19Hematology and Hemotherapy Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
20Department of Hematology, Hospital Universitario de Canarias, La Laguna, La Laguna, Spain
21Hospital de Bellvitge, Banc de Sang i Teixits, L´Hospitalet de Llobregat, Spain
22Hospital Juan R. Jiménez, Huelva, Spain
23Hospital Universitario de Basurto Osakidetza, Basurto, Spain
24Hospital Universitario Orense, ORENSE, Spain

Introduction: Autoimmune thrombotic thrombocytopenic purpura (aTTP) is a severe disease caused by the production of autoantibodies against von Willebrand factor (vWF)-cleaving ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin-1 motifs; 13th member of the family). Without functional ADAMTS13, endothelial cells-derived unusually large vWF (ULVWF) multimers are present and are responsible for platelet clumping in the microvasculature. Plasma exchange (PE) and immunosuppressive therapy with steroids and rituximab are the milestones of the treatment of this disease. Moreover, in 2018, nanobody caplacizumab was approved for the treatment of adult patients with an acute episode of aTTP. Our objective was to retrospectively review the efficacy and safety of the current use of caplacizumab in Spain.

Methods: We collected demographic, clinical, and laboratory data of patients with aTTP who were reported in the TTP Spanish Registry from 15 centres between July 2018 and July 2020. All patients were diagnosed with aTTP because of the presence of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, organ dysfunction, ADAMTS13 activity less than 5% and the presence of ADAMTS13 autoantibodies. Qualitative data are presented as number (frequencies). Quantitative data are presented as mean ± standard deviation (SD) or median (interquartile range –IQR-) when appropriate. A correlation test was performed to determine the linear relationship between number of days since diagnosis to caplacizumab start and number of days since diagnosis to the first day with >150x109/L platelets.

Results: Our series comprises 30 patients: 22 (73%) females and 8 (27%) males with a median age of 45 (IQR: 31-55). At presentation, neurologic abnormalities were seen in 18 (60%) patients, symptoms and signs of anemia were present in 15 (50%) patients, and bleeding was present in 10 (33%) patients. Fever was present in 1 (3%) patient. Laboratory tests showed hemoglobin 92±28 g/L, platelet count 19±16 x109/L, unconjugated bilirubin 2.33±1.76 mg/dL, LDH 1,467±1,428 IU/L, and creatinine 1.0±0.45 mg/dL. Median ADAMTS13 activity was 0 (IQR: 0-0.5) and ADAMTS13 autoantibodies were positive in all cases. After diagnosis, treatment was started with PE and steroids in all patients after a median of 0 days (IQR: 0-0) and patients received a median of 10 PE procedures (IQR: 7-13). Caplacizumab was administered to all patients with a median of 3 (IQR: 1-9) days after diagnosis and it was administered during 36 days (IQR: 31-39). No severe adverse events were reported with the use of caplacizumab. Rituximab was added in 19 (63%) patients after a median of 4 days (IQR: 14-21). Time to platelet normalization (>150x109/L) was 5.5 days (IQR: 4-17) after diagnosis. The longer the delay in administering caplacizumab after diagnosis, the longer the delay in platelet normalization (Pearson’s correlation coefficient, r=0.94 (95% CI: 0.86 to 0.98; R2=0.89; p<0.01; figure 1). Clinical remission was achieved in 29 (97%) patients after a median of 8 days (IQR: 4-14). One (3%) patient died because of aTTP complications 11 days after diagnosis. One patient was refractory to PE, steroids, rituximab, caplacizumab, and she achieved clinical remission after receiving vincristine and cyclophosphamide.

Conclusion: Caplacizumab was an efficacious and safe drug to treat adult patients with acute episodes of aTTP. A statistically significant strong positive linear correlation was observed between number of days from diagnosis to caplacizumab start and number of days from diagnosis to the first day with >150x109/L platelets.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH