OPTIMA: An Open-Label, Non-comparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection.

Abstract

RATIONALE:

Inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection.

OBJECTIVES:

This open label, non-comparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM (M. avium complex (MAC), M. abscessus (MABS)) infection, either in combination with ongoing guideline-based therapy (GBT), or as monotherapy in patients who had stopped GBT due to lack of efficacy or intolerability.

METHODS:

32 adult patients with refractory NTM (MAC 24, MABS 8) were recruited into two cohorts: with (16) or without (16) ongoing GBT. Nebulised molgramostim 300 μg/day was administered 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 3 consecutive monthly negative cultures during the treatment period.

RESULTS:

Eight patients (25%) achieved culture conversion on treatment (7 (29.2%) MAC patients, 1 (12.5%) MABS patient); in 4 patients this was durable after end of treatment. Of the 24 MAC patients, an additional four 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.

CONCLUSION:

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. There was less benefit seen in MABS. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.

TRIAL REGISTRY:

ClinicalTrials.gov No: NCT03421743.

• Authors: Rachel M Thomson, Michael R Loebinger, Andrew J Burke, Lucy C Morgan, Grant W Waterer, Cecilia Ganslandt
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) (Nov 10 2023) ISSN: 2325-6621 [Electronic] United States
• PMID: 37948736 (Publication Type: Journal Article)