伊布替尼
医学
威尼斯人
华登氏巨球蛋白血症
内科学
巨球蛋白血症
中性粒细胞减少症
肿瘤溶解综合征
胃肠病学
中止
不利影响
肿瘤科
白血病
化疗
慢性淋巴细胞白血病
淋巴瘤
多发性骨髓瘤
作者
Jorge J. Castillo,Andrew R. Branagan,David Sermer,Catherine Flynn,Kirsten Meid,Megan Little,Katherine Stockman,Timothy P. White,Alexa G Canning,Maria Luisa Guerrera,Amanda Kofides,Shirong Liu,Xia Liu,Kris Richardson,Nicholas Tsakmaklis,Christopher J. Patterson,Zachary Hunter,Steven P. Treon,Shayna Sarosiek
出处
期刊:Blood
[American Society of Hematology]
日期:2024-02-15
卷期号:143 (7): 582-591
被引量:1
标识
DOI:10.1182/blood.2023022420
摘要
Concurrent BTK and BCL2 inhibition has not been investigated in Waldenström macroglobulinemia. We performed an investigator-initiated trial of ibrutinib and venetoclax in symptomatic, treatment-naive patients with MYD88-mutated WM. Patients received ibrutinib 420 mg once daily (cycle 1), followed by a ramp-up of venetoclax to 400 mg daily (cycle 2). The combination was then administered for 22 additional four-week cycles. Attainment of VGPR was the primary endpoint. Forty-five patients were enrolled. Median baseline characteristics were age 67 years, serum IgM 43 g/L, and hemoglobin 102 g/L. Seventeen patients (38%) carried CXCR4 mutations. Nineteen patients (42%) achieved VGPR. Grade 3 or higher adverse events included neutropenia (38%), mucositis (9%), and tumor lysis syndrome (7%). Atrial fibrillation occurred in 3 (9%), and ventricular arrhythmia in 4 (9%) patients that included two grade 5 events. With median follow-up of 24.4 months, the 24-month progression-free (PFS) and overall survival (OS) rates were 76% and 96%, not impacted by CXCR4 mutations. Median time on therapy was 10.2 months, and median time after end of therapy (EOT) was 13.3 months. Eleven of the 12 progression events occurred after EOT, and the 12-month PFS rate after EOT was 79%; 93% if VGPR was attained, and 69% for other patients (p=0.12). Ibrutinib and venetoclax induced high VGPR rate and durable responses after EOT, though associated with a higher-than-expected rate of ventricular arrhythmia in WM patients leading to early study treatment termination. The trial was funded by Abbvie and Pharmacyclics (NCT04273139).
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