Use of inhaled GM-CSF in treatment-refractory NTM infection. An open-label, exploratory clinical trial

Inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment of non-tuberculous mycobacterial (NTM) infection. The aim of this pilot trial was to investigate the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) on treatment-refractory NTM (<i>M. avium</i>&nbsp;complex or&nbsp;<i>M. abscessus</i>) infection, either in combination with ongoing multidrug guideline-based therapy (GBT), or as a monotherapy in patients who had stopped GBT due to lack of efficacy or intolerability. 32 adult patients with chronic, culture positive NTM infection were recruited into two cohorts: with (14) or without (18) ongoing GBT. Inhaled GM-CSF 300 µg/day was given over 48 weeks. Sputum cultures and smears, and clinical assessments (6-Minute Walk Test, symptom scores, Quality of Life Questionnaire – Bronchiectasis, and body weight) were collected 4-weekly during treatment, and 12 weeks after end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive negative cultures during the treatment period. Five patients (15.6%) achieved culture conversion; in 2 patients it was durable after end of treatment. Among 29 smear positive patients, 11 (37.9%) achieved smear conversion (9 durable). Sputum and smear conversion rates were similar in the two cohorts. Clinical endpoints did not improve. 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, inhaled GM-CSF did not result in significant culture conversion rate, although a slight reduction in bacterial load was observed.