Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients.
Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients.
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DOI：
10.3324/haematol.2021.278901
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发表时间：
2022-06-01
期刊：
影响因子：
10.1
通讯作者：
Furman, Richard R.
中科院分区：
文献类型：
--
作者：
Brown, Jennifer R.;Byrd, John C.;Ghia, Paolo;Sharman, Jeff P.;Hillmen, Peter;Stephens, Deborah M.;Sun, Clare;Jurczak, Wojciech;Pagel, John M.;Ferrajoli, Alessandra;Patel, Priti;Tao, Lin;Kuptsova-Clarkson, Nataliya;Moslehi, Javid;Furman, Richard R.
布鲁顿酪氨酸激酶（BTK）抑制剂伊曲替尼的心血管（CV）毒性可能会限制这种有效疗法在慢性淋巴细胞白血病（CLL）患者中的应用。Acalabrutinib是第二代BTK抑制剂，BTK选择性更高。该分析描述了在临床试验中接受acalabrutinib单药治疗的CLL患者的合并CV不良事件（AE）数据（临床试验政府标识符：NCT 02029443、NCT 02475681、NCT 02970318和NCT 02337829）。Acalabrutinib口服给药，每日总剂量为100-400 mg，后来改为100 mg，每日两次，并持续至疾病进展或毒性。分析了762例患者的数据（中位年龄：67岁[范围：32-89];中位随访期：25.9个月[范围：0-58.5]）。129例患者（17%; ≥3级，n=37 [5%]）报告了任何级别的心脏AE，7例患者（1%）导致治疗中止。最常见的任何级别心脏AE为房颤/房扑（5%）、心悸（3%）和心动过速（2%）。总体而言，91%发生心脏AE的患者在acalabrutinib治疗前存在CV风险因素。在38例房颤/房扑事件患者中，7例（18%）有心律失常或房颤/房扑既往史。67例患者（9%）报告了高血压AE，其中43例（64%）有既存高血压病史;无患者因高血压停止治疗。未报告心源性猝死。总体而言，这些数据表明acalabrutinib治疗CLL患者新发心脏AE的发生率较低。在高危CLL患者中进行的一项头对头随机试验（临床试验政府标识符：NCT 02477696）的结果前瞻性评估了两种药物之间CV毒性的差异。
Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: NCT02029443, NCT02475681, NCT02970318 and NCT02337829). Acalabrutinib was given orally at total daily doses of 100–400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32–89]; median follow-up: 25.9 months [range, 0–58.5]) were analyzed. Cardiac AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with high-risk CLL (clinicaltrials gov. Identifier: NCT02477696) prospectively assess differences in CV toxicity between the two agents.
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DOI：
10.1200/jco.21.01210
发表时间：
2021-11-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Byrd JC;Hillmen P;Ghia P;Kater AP;Chanan-Khan A;Furman RR;O'Brien S;Yenerel MN;Illés A;Kay N;Garcia-Marco JA;Mato A;Pinilla-Ibarz J;Seymour JF;Lepretre S;Stilgenbauer S;Robak T;Rothbaum W;Izumi R;Hamdy A;Patel P;Higgins K;Sohoni S;Jurczak W
通讯作者：
Jurczak W
影响因子：
10.1
作者：
Brown JR;Moslehi J;O'Brien S;Ghia P;Hillmen P;Cymbalista F;Shanafelt TD;Fraser G;Rule S;Kipps TJ;Coutre S;Dilhuydy MS;Cramer P;Tedeschi A;Jaeger U;Dreyling M;Byrd JC;Howes A;Todd M;Vermeulen J;James DF;Clow F;Styles L;Valentino R;Wildgust M;Mahler M;Burger JA
通讯作者：
Burger JA
影响因子：
7.5
作者：
Awan, Farrukh T.;Schuh, Anna;Byrd, John C.
通讯作者：
Byrd, John C.
影响因子：
20.3
作者：
Byrd, John C.;Hillmen, Peter;Brown, Jennifer R.
通讯作者：
Brown, Jennifer R.
影响因子：
3.5
作者：
Archibald WJ;Rabe KG;Kabat BF;Herrmann J;Ding W;Kay NE;Kenderian SS;Muchtar E;Leis JF;Wang Y;Chanan-Khan AA;Schwager SM;Koehler AB;Fonder AL;Slager SL;Shanafelt TD;Call TG;Parikh SA
通讯作者：
Parikh SA