Among patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), caplacizumab with therapeutic plasma exchange (TPE) and immunosuppression appears to prevent unfavorable clinical outcomes, according to research published in Blood.
When left untreated, iTTP, a disease characterized by severe ADAMTS13 deficiency, is almost always fatal. Early diagnosis and treatment have, however, significantly improved survival, particularly since the advent of TPE and rituximab.
Caplacizumab, a nanobody targeting the A1 domain of ultra-large von Willebrand factor multimers, has been shown to improve some clinical measures in this disease setting, notably more rapid and durable recovery of platelet counts vs placebo, regardless of early rituximab intervention. In the present paper, researchers reported clinical findings in a group of patients with iTTP treated with compassionate-use caplacizumab. The primary outcome was refractoriness and death within 30 days of iTTP diagnosis; all patient data were reported to the French Reference Center for thrombotic microangiopathies.
Data from patients who received the triplet regimen (TPE, rituximab, and caplacizumab; 90 patients) were compared with a historical cohort (180 patients). In the triplet regimen and historical cohorts, the average ages were 45 and 43 years, respectively, 63 (70%) and 127 (70%) were women, 61% and 62% had cerebral involvement, and ADAMTS13 activity was less than 10% in both groups. Most baseline data were similar, though patients in the triplet regimen cohort had higher lactate dehydrogenase levels (5.1 vs 3.7 in the historical cohort; P =.01).
Patients in the historical cohort were more likely to have iTTP refractoriness or to die within 30 days of diagnosis (12.2% vs 2.2% in the triple regimen cohort; P =.01). According to the researchers, this suggested that patients receiving the triple regimen were 6.2 times less likely to have refractory disease or to die from iTTP (95% CI, 1.4-26.3; P =.013). A total of 12 patients (6.7%) died in the historical cohort vs 1 patient (1.1%) in the triple regimen cohort, though this difference was not significant (P =.06).
Patients in the triple regimen cohort also recovered platelet counts 1.8 times faster than did those in the historical cohort (P <.01); these patients also spent fewer days in hospital (13 vs 22; P <.01).
Adverse events related to caplacizumab occurred in 46 patients (51%), which included 13 “major or clinically relevant non-major hemorrhagic events.”
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Coppo P, Bubenheim M, Azoulay E, et al. A regimen with caplacizumab, immunosuppression and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood. Published online November 4, 2020. doi:10.1182/blood.2020008021