Shorter plasma exchange course may be safe with Cablivi in TTP
Small study found no worse short-term outcomes with fewer PEX sessions
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People with immune-mediated thrombotic thrombocytopenic purpura (TTP) taking Cablivi (caplacizumab) plus immunosuppressants may need fewer therapeutic plasma exchange sessions than previously thought, a small study suggests.
For years, standard treatment for immune TTP, a blood clotting disorder, has included immunosuppressants plus plasma exchange (PEX), a process that filters and replaces the liquid component of blood. Cablivi, an injection-based medication that blocks von Willebrand factor (VWF), a clotting protein involved in platelet clumping, is a newer addition to many treatment regimens.
In the small retrospective study, a shorter PEX course was not linked to worse short-term outcomes in people with immune TTP receiving early Cablivi and immunosuppression.
“These findings suggest that the addition of [Cablivi], and in particular early use of this [VWF-targeting] agent, has modified [immune] TTP … treatment paradigms in ways that have yet to be fully characterized,” the researchers wrote.
Cablivi may change plasma exchange needs
The study, “An Abbreviated Course of Therapeutic Plasma Exchange Does Not Affect Platelet Count Recovery or Durability in Patients With Immune Thrombotic Thrombocytopenic Purpura Receiving Caplacizumab,” was published in the Journal of Clinical Apheresis.
In immune TTP, the immune system mistakenly attacks ADAMTS13, an enzyme that normally helps prevent harmful blood clots from forming. This can result in clotting in small blood vessels and, if untreated, organ damage. Levels of platelets, blood fragments that play a role in clotting, also drop.
In immune TTP, PEX can remove disease-causing antibodies while providing functional ADAMTS13. Combined with immunosuppressants, PEX can help manage the disease. Cablivi was approved in the U.S. in 2019 to treat immune TTP in combination with PEX and immunosuppression.
“Incorporation of this novel therapeutic agent has been shown to more rapidly normalize platelet counts and decrease exacerbations, refractoriness, and mortality,” the researchers wrote.
Despite the more common use of Cablivi, the medical community has not rigorously reassessed protocols around immunosuppression and PEX in immune TTP. Often, patients undergo daily PEX until they have reached at least 150 billion platelets per liter of blood for at least two days.
The researchers noted that this convention is not based on high-quality studies or concrete clinical evidence. It is possible that people using Cablivi may be able to stop PEX earlier.
“For our patients with [immune] TTP … we had observed that platelet counts expectedly increased rapidly as they were receiving [Cablivi] and that the final 2 daily [PEX] procedures were being performed not for clinical concern but rather for perfunctory reasons,” the team noted.
To address this, they designed a study to compare the standard PEX protocol to an abbreviated protocol in patients receiving early Cablivi. Under the shorter protocol, participants stopped receiving PEX before reaching the threshold of 150 billion platelets/L.
Shorter PEX course not linked to worse outcomes
The study included 13 participants in the standard PEX group and 16 in the abbreviated PEX group. The average ages were 43 and 41 years in the two groups, respectively. The researchers identified the groups retrospectively, classifying participants based on when they stopped receiving PEX, according to medical records.
As expected, participants in the abbreviated group underwent significantly fewer PEX sessions than those in the standard group, with a mean of 3.2 versus 4.5 sessions.
Participants who had fewer sessions did not appear to have worse outcomes during follow-up. Over the 30 days after stopping daily PEX, they did not have a higher risk of death or disease worsening. No significant difference was seen in the share of patients whose ADAMTS13 activity was above 20% at 30 days.
Over the following six months, no participants in either group experienced a relapse.
The researchers suggested that these findings support re-examining how doctors define successful PEX treatment when patients are also taking Cablivi. “We posit that a platelet count of 150 [billion per liter] may no longer be a meaningful part of this definition,” they wrote.
Changing the definition to require fewer PEX sessions may help prevent patients from going through unnecessary procedures. An abbreviated PEX protocol might also allow for earlier discharge from the hospital in some cases.
“While the findings in the current study are preliminarily encouraging, limitations including its relatively small sample size and retrospective nature must be acknowledged,” the team wrote.
“We hope that the current study serves as an initial example for the need to continue to innovate, streamline, and optimize care for patients with [immune TTP] in the anti-vWF therapy era,” the investigators added.
