Treatment of acquired thrombotic thrombocytopenic purpura (aTTP) with caplacizumab, but without plasma exchange, increased platelet counts and improved surrogate parameters of organ damage in select patients, according to a report published in the Journal of Thrombosis and Haemostasis. These findings suggest that the anti–von Willebrand factor nanobody caplacizumab could possibly replace or delay the use of plasma exchange therapy in some patients.
“The current concepts and recommendations of aTTP treatment still see immediate daily plasma exchange as the most important therapy,” corresponding author Paul Knöbl, MD, of the Medical University of Vienna in Austria, told ASH Clinical News. “Plasma exchange was introduced around 1991 because there was no other option for aTTP at that time. Now, with caplacizumab, we have a highly specific drug directly targeting the formation of microthrombi, and that helps to keep patients safe from organ damage until immunosuppression kicks in and the autoantibodies to ADAMTS13 disappear.”
Dr. Knöbl added that, while plasma exchange has reduced mortality from higher than 90% to between 10 and 15%, some people still die from aTTP despite plasma exchange therapy. “Plasma exchange is time- and resource-consuming, and patients can still experience side effects, aTTP exacerbations, and complications,” he said. The development and approval of caplacizumab nearly 2 years ago transformed the treatment of aTTP, Dr. Knöbl said.
In this study, investigators retrospectively identified 6 women with aTTP who were treated with caplacizumab alone while enrolled in a trial of more than 60 patients evaluating caplacizumab plus plasma exchange. These patients experienced a total of seven aTTP episodes, and none received plasma exchange.
The 6 patients included in this analysis were all white women between the ages of 31 and 75 years. Moderate to severe organ dysfunction was observed in 4 participants, and 3 participants presented with a mild course of their disease.
Patients were treated with caplacizumab as soon as aTTP was either suspected or diagnosed. Treating physicians and patients opted to omit plasma exchange in lieu of the caplacizumab-only approach for a variety of reasons, including poor venous access, oligosymptomatic presentation, and refusal of consent to plasma exchange.
Treatment first consisted of caplacizumab 10 mg, which was administered as an intravenous injection, followed by 10 mg daily subcutaneous injections of the drug. There was a “rapid and robust” increase in platelet counts immediately following the first caplacizumab dose, the authors noted.
These increases ultimately resulted in the doubling of platelet counts within a median of 17 hours after treatment. In addition, platelet counts tripled after a median of 22 hours. Normalization of platelet counts (>150×109/L) occurred after a median of 84 hours.
Lactate dehydrogenase levels also improved during the time when platelet counts increased. Since lactate dehydrogenase represents a surrogate parameter of organ damage, the investigators suggested these findings indicate resolving microangiopathy in these caplacizumab-treated patients with aTTP.
All 6 patients recovered without treatment-related adverse event reactions or sequelae. Patients subsequently received immunosuppressive treatment with corticosteroids. While caplacizumab was continued until recovery of ADAMTS13 ≥10% activity in all patients, all but 1 patient recovered during the observation period. The median time to recovery in ADAMTS13 activity to ≥10% and ≥20% levels was 18 and 25 days, respectively.
“These results may be the key to completely changing clinical practice of aTTP management, as plasma exchange is, in fact, a very non-specific procedure that does not target the formation of platelet micro-clot formation leading to organ damage,” Dr. Knöbl concluded. However, the study’s findings are limited by its retrospective nature and the inclusion of a small, female patient population. The high cost of caplacizumab, especially in the U.S., represents a barrier to use.
“Our center and others have already changed aTTP treatment algorithms, trying to omit plasma exchange,” concluded Dr. Knöbl. “Future research will focus on optimizing timing, monitoring, and duration of caplacizumab therapy.” He added that this future research should also look at improving immunosuppression, and noted that the new International Society on Thrombosis and Haemostasis guidelines may soon need revision to include these data on caplacizumab therapy.
Study authors report relationships with Sanofi Genzyme, the manufacturer of caplacizumab.
Völker LA, Brinkkoetter PT, Knöbl PN, et al. Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab. J Thromb Haemost. 2020 August 5. [Epub ahead of print]