Coppo Paul, Bubenheim Michael, Azoulay Elie, Galicier Lionel, Malot Sandrine, Bigé Naïke, Poullin Pascale, Provôt François, Martis Nihal, Presne Claire, Moranne Olivier, Benainous Ruben, Dossier Antoine, Seguin Amélie, Hié Miguel, Wynckel Alain, Delmas Yahsou, Augusto Jean-François, Perez Pierre, Rieu Virginie, Barbet Christelle, Lhote François, Ulrich Marc, Rumpler Anne Charvet, de Witte Sten, Krummel Thierry, Veyradier Agnès, Benhamou Ygal
Centre de Référence des Microangiopathies Thrombotiques, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Service d'Hématologie, APHP Sorbonne Université, Paris, France.
Blood. 2021 Feb 11;137(6):733-742. doi: 10.1182/blood.2020008021.
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.
抗血管性血友病因子纳米抗体卡泊珠单抗基于前瞻性对照试验被批准用于治疗成人免疫性血栓性血小板减少性紫癜（iTTP）。然而，上市后监测的数据较少。我们采用了一种同情性一线三联疗法治疗了90例iTTP患者，该疗法联合了治疗性血浆置换（TPE）、使用皮质类固醇和利妥昔单抗进行免疫抑制以及使用卡泊珠单抗。将结果与180例接受标准一线治疗（TPE和皮质类固醇，使用利妥昔单抗作为挽救疗法）的历史患者进行了比较。主要结局是自诊断起30天内难治性和死亡的复合结局。关键次要结局包括病情加重、血小板计数恢复时间、TPE次数以及实现持久缓解所需的血浆量。三联疗法组出现复合主要结局的患者百分比为2.2%，而历史患者组为12.2%（P = 0.01）。三联疗法组中有1例老年患者死于肺栓塞。该队列中的患者病情加重情况较少（3.4%对44%，P < 0.01）；他们的血小板计数恢复持久的速度比历史患者快1.8倍（95%置信区间，1.41 - 2.36；P < 0.01），TPE次数更少且血浆量更低（两者P均< 0.01）。三联疗法组的住院天数比历史队列低41%（13天对22天；P < 0.01）。46例患者（51%）发生了与卡泊珠单抗相关的不良事件，包括13例严重或临床相关的非严重出血事件。通过针对iTTP病理生理学的三个过程，将卡泊珠单抗与TPE和免疫抑制联合使用，可预防不良结局并减轻护理负担。
