A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP

Abstract

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Graphical abstract

Figure 1.

The CAPLAVIE regimen. ADAMTS13 activity was assessed weekly until normalization or day 56.

Figure 2.

Flowchart of the study. *Mostly because of unawareness of practitioners about the availability of the compound (18 cases) or because patients were considered at risk of bleeding (1 case of recent surgery and 3 cases of active bleeding).

Figure 3.

Cumulative daily rate of platelet count recovery after first therapeutic plasma exchange within 35 days by cohort.

Figure 4.

Cumulative percentage of patients who achieved ADAMTS13 activity ≥ 20% after the last therapeutic plasma exchange in the triplet regimen (red columns) and the historical cohort (blue columns). ADAMTS13 activity was assessed weekly until normalization or day 56.