CAPLACIZUMAB INDUCES FAST AND DURABLE PLATELET COUNT RESPONSES WITH IMPROVED TIME TO COMPLETE REMISSION AND RECURRENCE-FREE SURVIVAL IN PATIENTS WITH ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA
Author(s): ,
Paul Coppo
Affiliations:
Department of Hematology,Reference Center for Thrombotic Microangiopathies (CNR-MAT), Saint-Antoine University Hospital, AP-HP,Paris,France
,
Marie Scully
Affiliations:
Cardiometabolic Programme, NIHR UCLH/UCL BRC, Department of Haematology,University College London Hospital,London,United Kingdom
,
Javier de la Rubia
Affiliations:
Hematology Department, Internal Medicine, School of Medicine and Dentistry,Catholic University of Valencia,Valencia,Spain;Hospital Doctor Peset,Valencia,Spain
,
Flora Peyvandi
Affiliations:
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italy;Department of Pathophysiology and Transplantation,Università degli Studi di Milano,Milan,Italy
,
Spero Cataland
Affiliations:
Division of Hematology, Department of Internal Medicine,The Ohio State University,Columbus, OH,United States
,
Johanna A. Kremer Hovinga
Affiliations:
Department of Hematology and Central Hematology Laboratory,Inselspital, Bern University Hospital, University of Bern,Bern,Switzerland
,
Paul Knoebl
Affiliations:
Division of Hematology and Hemostasis, Department of Medicine 1,Medical University of Vienna,Wien,Austria
,
Katerina Pavenski
Affiliations:
Departments of Medicine and Laboratory Medicine,St. Michael's Hospital, University of Toronto,Toronto, ON,Canada
,
Jessica Minkue Mi Edou
Affiliations:
Ablynx, a Sanofi company,Zwijnaarde,Belgium
,
Filip Callewaert
Affiliations:
Sanofi,Diegem,Belgium
Rui de Passos Sousa
Affiliations:
Sanofi,Lisbon,Portugal
(Abstract release date: 05/14/20) EHA Library. Coppo P. 06/12/20; 294110; EP1626
Paul Coppo
Paul Coppo
Contributions
Abstract

Abstract: EP1626

Type: e-Poster

Background
Acquired thrombotic thrombocytopenic purpura (aTTP) is characterized by disseminated platelet-rich microvascular occlusions throughout the body. Rapid control of platelet consumption and maintaining durable remission are key therapeutic goals. Many patients with aTTP experience exacerbation despite daily therapeutic plasma exchange (TPE) and immunosuppression.

In the Phase 3 HERCULES trial (NCT02553317), caplacizumab treatment resulted in a significantly faster time to platelet count normalization compared with placebo. Although some placebo-treated patients achieved a fast platelet count response, many subsequently progressed to rapid exacerbation of disease.

Aims
To characterize the durability of platelet count responses in the HERCULES trial.

Methods
In this post hoc analysis of the HERCULES intent-to-treat population (caplacizumab, n=72; placebo, n=73), we identified patients with a fast platelet count response (ie, ≤3 days vs >3 days) and described the exacerbation rate by treatment group. Time to durable platelet count response (defined as time to last daily TPE during the overall treatment period), time to complete remission (defined as platelet count >150×109/L and lactate dehydrogenase <1.5 × the upper limit of normal for >30 days after cessation of daily TPE), and recurrence-free survival (absence of exacerbation or relapse during the overall study period) were calculated.

Results
More than half of the patients in the HERCULES trial achieved an initial platelet count normalization within 3 days (caplacizumab, 56/72 [78%]; placebo, 43/73 [59%]). In patients with a fast platelet count response (ie, ≤3 days), the exacerbation rate was 3.6% (2/56) with caplacizumab and 44.2% (19/43) with placebo, suggesting that the rapid platelet count response was sustained with caplacizumab, whereas almost half of the fast responders in the placebo group subsequently exacerbated. In patients with time to platelet count response >3 days, the exacerbation rate was 6.7% (1/15) with caplacizumab and 30.0% (9/30) with placebo, confirming the durable response with caplacizumab. The exacerbation rate among placebo patients with platelet response >3 days remained high but was numerically lower compared with fast responders. Of the patients who experienced exacerbations, 90% (2/3 in the caplacizumab group and 26/28 in the placebo group) switched to open-label caplacizumab, which may have favored the outcomes of placebo patients. Despite this bias, the median (95% CI) time to durable response was 4.5 (4.4–4.6) days with caplacizumab and 10.5 (6.5–14.5) days with placebo (Figure 1A); accordingly, the median (95% CI) time to complete remission was shorter in the caplacizumab group (40.0 [37.7–41.1] days) compared with placebo (44.2 [42.0–48.2] days) (Figure 1B). The analysis of overall recurrence-free survival during the entire study period demonstrated an early and sustained benefit for caplacizumab over placebo (Figure 1C), mainly driven by significant reduction in exacerbations during the study drug treatment period. The effect was sustained, despite six relapses in the caplacizumab group in the follow-up period in patients with unresolved underlying autoimmune disease activity.

Conclusion
Caplacizumab demonstrated a faster and sustained platelet count response compared with the placebo group, in which many fast responders subsequently had an exacerbation. Fast platelet count responses with caplacizumab were maintained and translated into clinically relevant improvements in time to complete remission and overall recurrence-free survival.

Session topic: 32. Platelets disorders

Keyword(s): Clinical trial, Platelet count, Recurrence, Thrombotic thrombocytopenic purpura (TTP)

Abstract: EP1626

Type: e-Poster

Background
Acquired thrombotic thrombocytopenic purpura (aTTP) is characterized by disseminated platelet-rich microvascular occlusions throughout the body. Rapid control of platelet consumption and maintaining durable remission are key therapeutic goals. Many patients with aTTP experience exacerbation despite daily therapeutic plasma exchange (TPE) and immunosuppression.

In the Phase 3 HERCULES trial (NCT02553317), caplacizumab treatment resulted in a significantly faster time to platelet count normalization compared with placebo. Although some placebo-treated patients achieved a fast platelet count response, many subsequently progressed to rapid exacerbation of disease.

Aims
To characterize the durability of platelet count responses in the HERCULES trial.

Methods
In this post hoc analysis of the HERCULES intent-to-treat population (caplacizumab, n=72; placebo, n=73), we identified patients with a fast platelet count response (ie, ≤3 days vs >3 days) and described the exacerbation rate by treatment group. Time to durable platelet count response (defined as time to last daily TPE during the overall treatment period), time to complete remission (defined as platelet count >150×109/L and lactate dehydrogenase <1.5 × the upper limit of normal for >30 days after cessation of daily TPE), and recurrence-free survival (absence of exacerbation or relapse during the overall study period) were calculated.

Results
More than half of the patients in the HERCULES trial achieved an initial platelet count normalization within 3 days (caplacizumab, 56/72 [78%]; placebo, 43/73 [59%]). In patients with a fast platelet count response (ie, ≤3 days), the exacerbation rate was 3.6% (2/56) with caplacizumab and 44.2% (19/43) with placebo, suggesting that the rapid platelet count response was sustained with caplacizumab, whereas almost half of the fast responders in the placebo group subsequently exacerbated. In patients with time to platelet count response >3 days, the exacerbation rate was 6.7% (1/15) with caplacizumab and 30.0% (9/30) with placebo, confirming the durable response with caplacizumab. The exacerbation rate among placebo patients with platelet response >3 days remained high but was numerically lower compared with fast responders. Of the patients who experienced exacerbations, 90% (2/3 in the caplacizumab group and 26/28 in the placebo group) switched to open-label caplacizumab, which may have favored the outcomes of placebo patients. Despite this bias, the median (95% CI) time to durable response was 4.5 (4.4–4.6) days with caplacizumab and 10.5 (6.5–14.5) days with placebo (Figure 1A); accordingly, the median (95% CI) time to complete remission was shorter in the caplacizumab group (40.0 [37.7–41.1] days) compared with placebo (44.2 [42.0–48.2] days) (Figure 1B). The analysis of overall recurrence-free survival during the entire study period demonstrated an early and sustained benefit for caplacizumab over placebo (Figure 1C), mainly driven by significant reduction in exacerbations during the study drug treatment period. The effect was sustained, despite six relapses in the caplacizumab group in the follow-up period in patients with unresolved underlying autoimmune disease activity.

Conclusion
Caplacizumab demonstrated a faster and sustained platelet count response compared with the placebo group, in which many fast responders subsequently had an exacerbation. Fast platelet count responses with caplacizumab were maintained and translated into clinically relevant improvements in time to complete remission and overall recurrence-free survival.

Session topic: 32. Platelets disorders

Keyword(s): Clinical trial, Platelet count, Recurrence, Thrombotic thrombocytopenic purpura (TTP)

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