#1491 Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange
Authors: Kühne Lucas , Knöbl Paul , Eller Kathrin , Völker Linus , Brinkkötter Paul 
Published: May 2024

Abstract

Background and Aims
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. The anti-VWF nanobody Caplacizumab is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. This study evaluates the treatment of acute iTTP with caplacizumab and immunosuppression, but without TPE, in comparison to the conventional management with TPE, caplacizumab and immunosuppression.

Method
All patients in this study were identified from the Austrian Thrombotic Microangiopathy Registry (ATMAR) and the German REACT-2020 TTP registry (ClinicalTrials.gov identifier: NCT04985318). A total of 42 acute iTTP episodes in 41 patients were managed with a treatment regimen aimed at avoiding first-line TPE if the platelet count increased after the first dose of 10 mg caplacizumab, and the patient's condition and organ function remained stable (TPE-free cohort). This treatment modification was implemented based on shared decision making.
An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 iTTP patients, receiving frontline caplacizumab treatment with TPE and immunosuppression (TPE cohort). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractoriness, and iTTP-related deaths.

Results
The primary outcome parameter, time to platelet count normalization, was not significantly different between TPE-free and TPE-based management (Kaplan-Meier estimator and log-rank test, Table 1 and Fig. 1). The median time to platelet count normalization was 3 days in the TPE-free cohort and 4 days in the TPE cohort.
There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths. For evaluation of the short-term treatment response, both cohorts were assessed for the time to platelet count doubling. The median time to platelet count doubling was 1 day in both cohorts.
Four patients in the TPE-free cohort did not immediately respond to the first caplacizumab injection and subsequently underwent TPE, after a maximum monitoring period of 40 hours. In these patients, TPE was initiated at a median of 1.5 days after the first caplacizumab dose, and TPE was performed for a median of 4.5 days. This delayed platelet response could be attributed to concomitant diseases and factors, e.g. active HIV and hepatitis B virus coinfection, active CMV infection, concomitant antiplatelet antibodies in association with an ovarian teratoma, and multiple platelet transfusions before the correct diagnosis.
During overall follow-up, complications were observed in 11 patients (26.2%) in the TPE-free group and 16 patients (27.1%) in the TPE group, excluding complications of iTTP that were evaluated as outcome parameters. Serious complications occurred in 4 patients (6.8%) from the TPE cohort while on TPE, including severe systemic anaphylactic reactions with severe hypotension, generalized seizure and supraventricular tachycardia. Bleeding complications were reported without a significant difference between groups.

Conclusion
For the first time since the introduction of TPE in the early 1990s, the results of our study systematically challenge the absolute need for TPE and suggest a paradigm shift in acute iTTP management.
In detail, our treatment approach was successfully implemented in 38 of 42 acute iTTP episodes (90.5%). We observed no significant difference in the time to platelet count normalization between patients with iTTP treated with and without TPE. The analysis of key secondary outcomes did not reveal significant differences in the proportion of patients who achieved a clinical response or experienced exacerbations, refractoriness, or TTP-related deaths.
In conclusion, Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP.