Highlights from

ATS 2019

American Thoracic Society international conference

Dallas, USA 17-22 May 2019

Stem cell therapy in acute respiratory distress syndrome improves 28-day mortality

Dr Geoff Bellingan (University College London, United Kingdom) presented the early-stage study results from the exploratory phase 1/2 trial in patients with acute respiratory distress syndrome (ARDS): the MUST-ARDS trial. The take-home message was that the ex vivo adult progenitor cell-expanding therapy can improve 28-day mortality, lessened ventilator and ICU burden, and demonstrated overall safety in patients with ARDS [1].

Subjects in the exploratory study were evaluated for 28 days for the primary clinical assessment and will be further assessed for a 1-year follow-up period. The MultiStemTM stem treatment group achieved the primary endpoint of safety. The treatment was well-tolerated and, no serious adverse events were observed.

Treatment was required to begin within 4 days of ARDS diagnosis with an average treatment time of approximately 2 days after the diagnosis. Initially, 3 subjects received 300 million stem cells and, after a safety review, an additional 3 subjects received 900 million stem cells. This was followed by the larger double-blinded, placebo-controlled, and randomised study of 20 subjects treated with an intravenous (IV) administration of 900 million stem cells and 10 subjects receiving IV placebo. The researchers employed a prospectively-defined analysis examining the effects on subjects with poorer lung function as determined by a ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2) of <150, reporting that the difference between stem treatment and placebo was greater than that observed in the intention-to-treat population. There was 25% mortality in the MultiStem group vs 50% in the placebo group, 14.6 ventilator-free days in the MultiStem group vs 8.0 ventilator-free days in the placebo group, and 11.4 intensive care unit-free days in the MultiStem group vs 5.9 ICU-free days in the placebo group. The median values of the data set were 18.5 ventilator-free days for the MultiStem-treated patients compared with 3.5 ventilator-free days for the placebo group, and 12.5 ICU-free days for MultiStem patients compared with 1 ICU-free day for the placebo group. There was an overall reduction in certain acute inflammatory cytokines in the MultiStem treatment group compared with the placebo group, which may potentially represent relevant biomarkers, requiring further validation.

Dr Bellingan discussed potential mechanisms by which MultiStem may be providing benefit to ARDS patients, such as through restored endothelial integrity of the lung, reduced lung oedema, increased alveolar fluid clearance, reduced immune cell infiltrate (including neutrophils, macrophages, and eosinophils), and the ability to shift immune cells from a pro-inflammatory to anti-inflammatory phenotype. “ARDS is more common than people realise, and there is no cure for it because it is a heterogeneous condition,” commented he commented. “The data from the MUST-ARDS trial is very encouraging, and I am looking forward to having a potential therapy to offer ARDS patients.”

Keywords: stem cell therapy, acute respiratory distress syndrome, ARDS, MUST-ARDS trial.

  1. Bellingan G, et al. A7353, ATS 2019, 17-22 May, Dallas, USA.

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