Table 2.
Summary of randomized clinical trials assessing inhaled GM-CSF versus placebo in patients with autoimmune pulmonary alveolar proteinosis
| Author, journal, year, trial name | GM-CSF molecule | Dose and duration | After WLL | Number of patients | Efficacy |
|---|---|---|---|---|---|
|
Tazawa et al., N Engl J Med, 2019, PAGE trial [34] |
Sargramostim |
125 µg ×2/jday for 7 days, every other week for 24 weeks |
No |
63 33 GM-CSF 30 placebo |
Positive primary endpoint: significant decrease in AaDO2: 4.50 ± 9.03 mm Hg vs 0.17 ± 10.50 mm Hg, p = 0.02 Significant decrease in lung density on a chest CT scan No significant improvement in QoL (CAT questionnaire), FVC, DLCO, and 6MWT |
| Tian et al., Orphanet J Rare Dis, 2020 [35] | Molgramostim | 150 µg ×2/day for 7 days, every other week for 3 months followed by 150 µg ×1/jday for 7 days, every other week for 3 months, for a total of 6 months (with an additional follow-up of 24 months) | No |
36 19 GM-CSF 17 placebo |
Negative primary endpoint: no significant decrease in AaDO2: 7.31 ± 8.81 mm Hg vs 1.8 ± 11.21 mm Hg, p = 0.146 (6 months) Significant improvement of QoL (SGRQ) at 6 and 24 months, TLC, and DLCO only at 24 months No efficacy on a chest CT scan or number of rescue WLLs |
| Trapnell et al., N Engl J Med, 2020, IMPALA trial [37] | Molgramostim | 300 µg ×1/day either: daily (continuous arm), or for 7 days, every other week (intermittent arm) for 24 weeks | No |
138 46 continuous GM-CSF 45 intermittent GM-CSF 47 placebo |
Positive primary endpoint in continuous inhaled GM-CSF arm: significant decrease in AaDO2: − 12.8 mmHg vs − 6.6 mmHg; mean difference − 6.2 mm Hg, p = 0.03 Significant improvement of all other endpoints in the continuous arm: QoL (SGRQ), DLCO, a decrease in number of rescue WLLs, and a decrease in ground glass opacity score on a chest CT scan |
|
Campo et al., Eur Respir J, 2024 [32] |
Sargramostim |
250 µg ×1/day for 7 days, every other week for 12 weeks followed by 4 weeks of washout, and then 250 µg ×1/jday on day 1 and day 3 every 14 days for 6 months For a total of 10 months |
Yes (initiated within 7 days after WLL) |
18 9 GM-CSF 9 placebo |
Positive primary endpoint: increase of median time to rescue WLLs in GM-CSF arm compared with placebo: 18 (IQR 6, 27) months vs 30 (30, 30) months, p < 0.0078 Significant decrease in AaDO2, PaO2, and DLCO Non-significant decrease in lung density on a chest CT scan and non-significant improvement of QoL (SF-36) |
| Trapnell, N Engl J Med, 2025, IMPALA-2 trial [36] | Molgramostim | 300 µg ×1/day for 48 weeks | No |
164 81 GM-CSF 83 placebo |
Positive primary endpoint: significant increase in DLCO at week 24: mean difference +6.0 mm Hg, p = 0.0007 Significant improvement of numerous other endpoints: DLCO at week 48 (change from baseline 11.60% vs 4.70%; estimated treatment difference, 6.90%; p = 0.0008), QoL (SGRQ), AaDO2, DSS, decrease in ground glass opacity score on a chest CT scan, improvement of exercise capacity on a treadmill |
6MWT Six-Minute Walk Test, AaDO2 alveolo-arterial difference in oxygen, CAT questionnaire COPD assessment test questionnaire, DLCO diffusion of carbon monoxide, DSS disease severity score, FVC forced vital capacity, GM-CSF granulocyte-macrophage colony-stimulating factor, IQR interquartile range, PaO2 partial pressure of oxygen, QoL quality of life, SGRQ St George Respiratory Questionnaire, TLC total lung capacity, WLL whole lung lavage