Jeff P Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, Krish Patel, Ian W Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Marie Hughes, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, George Follows, Patricia Walker, Paolo Ghia, Ann Janssens, John C Byrd, Emmanuelle Ferrant, Alessandra Ferrajoli, William G Wierda, Catherine Wangui Wachira, Batul T Suterwala, Paulo Miranda, Veerendra Munugalavadla, Chuan-Chuan Wun, Jennifer A Woyach
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引用次数: 0
摘要
阿卡拉布替尼是一种布鲁顿酪氨酸激酶抑制剂，被批准用于治疗慢性淋巴细胞白血病。在中位随访74.5个月后，我们报告了ELEVATE-TN （NCT02475681）的结果。总体而言，535名患者被随机分配(阿卡鲁替尼-比努妥珠单抗，n = 179；Acalabrutinib, n = 179；氯霉素-比努妥珠单抗，n = 177)。中位年龄为70岁，63.0%为未突变的IGHV（维吾尔v）， 13.6%为del（17p）和/或突变的TP53, 17%为复杂核型(CK；染色体异常≥3例)。阿卡鲁替尼和阿卡鲁替尼的中位无进展生存期（PFS）未达到（NR），而氯霉素-阿卡鲁替尼的中位无进展生存期为27.8个月（P均< 0.0001）；估计72个月的总体PFS率分别为78.0%、61.5%和17.2%。阿卡鲁替尼-obinutuzumab与阿卡鲁替尼单药治疗相比改善了PFS（风险比[HR]: 0.58, P = 0.0229）。有维吾尔病毒、del（17p）和/或突变TP53或CK的患者，阿卡拉布替尼±比布努妥珠单抗与氯布西-比布妥珠单抗相比，PFS显著改善（P < 0.0001, P≤0.0009,P < 0.0001）。所有治疗的中位总生存期（OS）均为NR，阿卡鲁替尼-比比布西-比比妥珠单抗的OS明显更长（HR: 0.62, P = 0.0349）。阿卡鲁替尼-比努妥珠单抗、阿卡鲁替尼和氯苯布西-比努妥珠单抗的估计72个月OS率分别为83.9%、75.5%和74.7%。4年后发生的不良事件（ae）以1-2级为主。阿卡鲁替尼组的不良事件发生率、严重不良事件发生率和临床兴趣事件发生率相似，与阿卡鲁替尼和奥比妥珠单抗的已知安全性一致。含阿卡鲁替尼组的疗效和安全性得到维持，包括高危患者在内，阿卡鲁替尼组与氯苯布西-比努单抗组的PFS均较长。
Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN.
Abstract: Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.
期刊介绍：
Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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