Thomson Rachel M, Loebinger Michael R, Burke Andrew J, Morgan Lucy C, Waterer Grant W, Ganslandt Cecilia
School of Clinical Medicine, University of Queensland, Brisbane, Queensland, Australia.
Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, Australia.
Ann Am Thorac Soc. 2024 Apr;21(4):568-576. doi: 10.1513/AnnalsATS.202306-532OC.
Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection. This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection ( complex [MAC] and [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability. Thirty-two adult patients with refractory NTM infection (MAC, = 24; MABS, = 8) were recruited into two cohorts: those with ( = 16) and without ( = 16) ongoing GBT. Nebulized molgramostim 300 μg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period. Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported. In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).
吸入粒细胞-巨噬细胞集落刺激因子（GM-CSF）已被提议作为非结核分枝杆菌（NTM）感染的一种潜在免疫调节治疗方法。这项开放标签、非对照的试点试验研究了吸入GM-CSF（莫拉司亭雾化溶液）对主要为难治性肺部NTM感染（鸟分枝杆菌复合群[MAC]和偶然分枝杆菌[MABS]）患者的疗效和安全性，这些患者要么联合正在进行的基于指南的治疗（GBT），要么作为因疗效不佳或不耐受而停止GBT的患者的单一疗法。32例难治性NTM感染成年患者（MAC，n = 24；MABS，n = 8）被纳入两个队列：接受正在进行的GBT的患者（n = 16）和未接受GBT的患者（n = 16）。在48周内给予雾化莫拉司亭300μg/d。在治疗期间每4周以及治疗结束后12周收集痰培养、涂片和临床评估（6分钟步行距离、症状评分、支气管扩张症生活质量问卷评分和体重）。主要终点是痰培养转阴，定义为治疗期间连续三个月痰培养阴性。8例患者（25%）在治疗期间实现了培养转阴（7例[29.2%]MAC感染患者，1例[12.5%]MABS感染患者）；4例患者在治疗结束后仍保持转阴。在24例MAC感染患者中，另外4例患者有部分反应，从基线时涂片阳性转为治疗结束时涂片阴性，液体培养基中阳性时间延长。其中2例患者从治疗结束后痰培养一直保持阴性。其他临床终点未改变。严重不良事件主要是肺部加重或NTM感染恶化。报告了3例与治疗无关的死亡。在这一严重NTM疾病患者群体中，莫拉司亭安全且耐受性良好。MAC感染患者的痰培养转阴率（29.2%）高于仅接受GBT治疗的类似难治性MAC队列报告的转阴率。MABS感染患者获益较少。未发现严重安全问题。有必要在更大队列中进行进一步评估。临床试验已在www.clinicaltrials.gov注册（NCT03421743）。
