A Regimen with Caplacizumab, Immunosuppression, and Plasma Exchange Prevents Unfavorable Outcomes in Immune-Mediated TTP
On February 11, 2021 in the journal Blood, investigators reported on the real world experience with caplacizumab in immune mediated TTP, in combination with immunosuppression and plasma exchange. The Von Willebrand Factor targeting monoclonal antibody caplacizumab has been approved for adults with immune mediated TTP based on prospective controlled trials.
Because there is a lack of post-marketing surveillance data, the investigators wanted to compare 90 patients that were treated with a compassionate frontline triplet regimen comprising caplacizumab, therapeutic plasma exchange, immunosuppression with corticosteroids to historical controls. The outcomes were compared with the 180 historical patients treated with what the authors described as standard frontline treatment including therapeutic plasma exchange, corticosteroids, rituximab as salvage therapy. The primary outcome was a composite of refractoriness as well as death within 30 days since diagnosis.
Key secondary outcomes were exacerbation, time to platelet count recovery, the number of therapeutic plasma exchanges in the volume of plasma required to achieve durable remission. The percentage of patients in the triple arm with a composite primary outcome was 2.2 versus 12.2%. This is in comparison to historical patients, P = 0.01. 1 elderly patient was reported to have died in the triple regimen as a result of a pulmonary embolus. Patients from this cohort experienced less exacerbations, 3.4% versus 44%, P < 0.01.
The authors claim that patients recover durable platelet counts 1.8 times faster than historical patients, with fewer therapeutic plasma exchange sessions and lower plasma volumes, P < 0.01 for both. With regards to the number of days in the hospital, 41% lower in the triple regimen compared to historical controls, 13 versus 22 days, P < 0.01. Caplacizumab associated adverse events were seen in 51%, 46 patients, including 13 major or clinically relevant nonmajor hemorrhagic events.
The authors concluded “associating caplqcizumab to therapeutic plasma exchange and immunosuppression, by addressing the 3 processes of immune mediated TTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care”