Kết quả dài hạn từ nghiên cứu COMFORT-II, thử nghiệm giai đoạn 3 của ruxolitinib so với liệu pháp tốt nhất có sẵn cho bệnh xơ tủy

Leukemia - Tập 30 Số 8 - Trang 1701-1707 - 2016
Claire Harrison1, Alessandro M. Vannucchi2, Jean‐Jacques Kiladjian3, Haifa Kathrin Al‐Ali4, Heinz Gisslinger5, Laurent Knoops6, Francisco Cervantes7, Mark M. Jones8, Kang Sun8, Mari McQuitty9, Viktoriya Stalbovskaya9, Prashanth Gopalakrishna9, Tiziano Barbui10
1Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK
2Department of Experimental and Clinical Medicine, Center for Research and Innovation for Myeloproliferative Neoplasms-CRIMM, AOU Careggi, University of Florence, Florence, Italy
3Hôpital Saint-Louis et Université Paris Diderot, Paris, France
4University of Leipzig, Leipzig, Germany
5Medical University of Vienna, Vienna, Austria
6Cliniques Universitaires Saint-Luc and de Duve Institute, Université catholique de Louvain, Brussels, Belgium
7Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
8Incyte Corporation, Wilmington, DE, USA.
9Novartis Pharma, Basel, Switzerland
10Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy

Tóm tắt

Tóm tắt

Ruxolitinib là một chất ức chế Janus kinase (JAK) (JAK1/JAK2) đã cho thấy sự vượt trội hơn so với giả dược và liệu pháp tốt nhất có sẵn (BAT) trong các nghiên cứu Controlled Myelofibrosis Study với điều trị bằng thuốc uống ức chế JAK (COMFORT). COMFORT-II là một nghiên cứu pha 3 ngẫu nhiên (2:1), mở tại những bệnh nhân bị xơ tủy; những bệnh nhân được phân ngẫu nhiên vào nhóm BAT có thể chuyển sang ruxolitinib khi bệnh tiến triển theo định nghĩa của giao thức hoặc sau kết thúc điểm chính, làm phức tạp so sánh dài hạn. Vào tuần thứ 48, 28% (41/146) bệnh nhân được phân ngẫu nhiên vào ruxolitinib đạt được giảm ⩾35% khối lượng lách (điểm chính) so với không có bệnh nhân nào ở BAT (P<0.001). Trong số 78 bệnh nhân (53.4%) trong nhánh ruxolitinib đạt được giảm ⩾35% khối lượng lách bất kỳ lúc nào, xác suất duy trì đáp ứng là 0.48 (khoảng tin cậy (CI), 0.35–0.60) sau 5 năm (trung vị, 3.2 năm). Trung vị thời gian sống toàn bộ chưa được đạt ở nhánh ruxolitinib và là 4.1 năm ở nhánh BAT. Có giảm 33% nguy cơ tử vong với ruxolitinib so với BAT theo phân tích ý định điều trị (tỷ lệ nguy cơ (HR) = 0.67; CI 95%, 0.44–1.02; P = 0.06); HR điều chỉnh chéo là 0.44 (CI 95%, 0.18–1.04; P = 0.06). Không có sự gia tăng không mong đợi về tỷ lệ mắc phải tác dụng phụ với thời gian dùng lâu hơn. Phân tích cuối cùng này cho thấy rằng các giảm khối lượng lách với ruxolitinib được duy trì với liệu pháp tiếp tục và có thể liên quan đến lợi ích sống còn.

Từ khóa

#ruxolitinib #Janus kinase ức chế #xơ tủy #COMFORT-II #khối lượng lách #tỷ lệ sống còn #phân tích giai đoạn 3 #nguy cơ tử vong #tác dụng phụ

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Leukemia

Tập 30 Số 8

1701-1707

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