PB1325 - Recurrent thrombocytopenia during caplacizumab treatment in patients with acute immune-mediated thrombotic thrombocytopenic purpura after the clinical response

Background: Caplacizumab, an anti-von Willebrand Factor (VWF) nanobody, has significantly accelerated the normalization of platelet counts and reduced acute mortality in immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, some cases have experienced recurrent thrombocytopenia during the caplacizumab therapy after the clinical response.

Aims: To investigate the clinical and laboratory parameters in caplacizumab-treated patients experiencing recurrent thrombocytopenia that required additional treatment during the caplacizumab therapy.

Methods: We analyzed acute iTTP patients in our TMA registry who were treated with caplacizumab following its approval in Japan in December 2022. Of those, nineteen patients who had ADAMTS13 activity or inhibitor measured at least once a week were included in this study. Laboratory data, including ADAMTS13-related parameters, were examined in this cohort.

Results: At the onset, ADAMTS13 activity was below 0.5% in all cases, with a median ADAMTS13 inhibitor level of 7.1 Bethesda Unit (BU)/mL. Platelet counts reached over 150×109 /L in all cases, with a median duration of 6 days to achieve this. Six patients experienced a recurrence of thrombocytopenia during the caplacizumab treatment and required additional therapy (defined as the intensified treatment group). VWF multimer analysis of representative patients is shown in Figure 1. The median lowest platelet count in this group was 48×109 /L, occurring at a median of 23 days. Additional treatments included therapeutic plasma exchange (n=3), plasma infusion (n=1), rituximab (n=2), steroid pulse (n=1), and cyclophosphamide (n=1). Although not statistically significant, the median duration for ADAMTS13 activity to recover to over 10% tended to be longer in the intensified treatment group (42 days) compared to the non-intensified group (30 days, p=0.124).

Conclusion(s): While there is currently no international consensus on defining worsening iTTP disease during the caplacizumab treatment, we found that recurrent thrombocytopenia occurred at a certain rate. Monitoring ADAMTS13-related parameters, along with platelet counts, is crucial during caplacizumab therapy.