背景:在过去的十年中,Ibrutinib已成为治疗几种淋巴增殖性疾病的标准护理,例如慢性淋巴细胞白血病(CLL)和几种非霍奇金淋巴瘤。超越布鲁顿酪氨酸激酶抑制,Ibrutinib显示广泛的免疫调节作用,可能促进感染性并发症的发生,包括机会性感染.已显示传染病负担因疾病状况而异,中性粒细胞减少症,和以前的治疗,但有关需要重症监护病房(ICU)入院的严重感染的数据仍然很少。我们试图调查2015年1月1日至2020年12月31日在10个法国重症监护病房(ICU)接受ibrutinib治疗的69名患者的多中心队列中严重感染的特征和结局。
结果:伊布替尼开始的中位时间为6.6[3-18]个月。侵袭性真菌感染占严重感染的19%(n=13/69),包括9例(69%;n=9/13)侵袭性曲霉病,3(23%;n=3/13)肺孢子虫肺炎,1例(8%;n=1/13)隐球菌病。最常见的器官损伤是急性呼吸衰竭(ARF)(71%;n=49/69),41%(n=28/69)的患者需要机械通气。20例(29%;n=20/69)患者在ICU死亡,而90天的死亡率达到55%(n=35/64)。与幸存者相比,死者表现出更严重的器官功能障碍(SOFA7[5-11]与4[3-7],p=0.004),并且更有可能接受机械通气(68%vs.31%,p=0.010)。根据年龄和潜在的恶性肿瘤,将63名依鲁替尼治疗的患者与来自历史队列的63名接受常规化疗的对照进行匹配。尽管先前化疗行的中位数较高(2[1-2]与0[0-2];p<0.001)和更高的真菌发生率[21%vs.8%,p=0.001和病毒[17%vs.5%,p=0.027]接受ibrutinib的患者感染,ICU(27%vs.38%,p=0.254)和90天死亡率(52%vs.48%,p=0.785)两组之间相似。
结论:在依鲁替尼治疗的患者中,需要入住ICU的严重感染与不良预后相关,主要受最初器官衰竭的影响。在这种免疫功能低下的人群中,ICU临床医生应系统地筛查机会因子。
BACKGROUND: In the last decade, Ibrutinib has become the standard of care in the treatment of several lymphoproliferative diseases such as chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphoma. Beyond Bruton tyrosine kinase inhibition, Ibrutinib shows broad immunomodulatory effects that may promote the occurrence of infectious complications, including opportunistic infections. The infectious burden has been shown to vary by disease status, neutropenia, and prior therapy but data focusing on severe infections requiring intensive care unit (ICU) admission remain scarce. We sought to investigate features and outcomes of severe infections in a multicenter cohort of 69 patients receiving ibrutinib admitted to 10 French intensive care units (ICU) from 1 January 2015 to 31 December 2020.
RESULTS: Median time from ibrutinib initiation was 6.6 [3-18] months. Invasive fungal infections (IFI) accounted for 19% (n = 13/69) of severe infections, including 9 (69%; n = 9/13) invasive aspergillosis, 3 (23%; n = 3/13) Pneumocystis pneumonia, and 1 (8%; n = 1/13) cryptococcosis. Most common organ injury was acute respiratory failure (ARF) (71%; n = 49/69) and 41% (n = 28/69) of patients required mechanical ventilation. Twenty (29%; n = 20/69) patients died in the ICU while day-90 mortality reached 55% (n = 35/64). In comparison with survivors, decedents displayed more severe organ dysfunctions (SOFA 7 [5-11] vs. 4 [3-7], p = 0.004) and were more likely to undergo mechanical ventilation (68% vs. 31%, p = 0.010). Sixty-three ibrutinib-treated patients were matched based on age and underlying malignancy with 63 controls receiving conventional chemotherapy from an historic cohort. Despite a higher median number of prior chemotherapy lines (2 [1-2] vs. 0 [0-2]; p < 0.001) and higher rates of fungal [21% vs. 8%, p = 0.001] and viral [17% vs. 5%, p = 0.027] infections in patients receiving ibrutinib, ICU (27% vs. 38%, p = 0.254) and day-90 mortality (52% vs. 48%, p = 0.785) were similar between the two groups.
CONCLUSIONS: In ibrutinib-treated patients, severe infections requiring ICU admission were associated with a dismal prognosis, mostly impacted by initial organ failures. Opportunistic agents should be systematically screened by ICU clinicians in this immunocompromised population.