MAVRILIMUMAB IMPROVES OUTCOMES IN SEVERE COVID-19 PNEUMONIA AND SYSTEMIC HYPER-INFLAMMATION

Background:Patients with severe COVID-19 pneumonia and hyperinflammation face increased mortality There is an urgent need for effective treatments to reduce the burden of the COVID-19 pandemic Objectives:Our protocol aimed at evaluating the potential improvement in clinical outcomes with mavrilimumab, an anti-Granulocyte/Macrophage Colony-Stimulating Factor Receptor alpha (GM-CSFRα) monoclonal antibody, in patients with COVID-19 pneumonia and systemic hyper-inflammation Methods:Single-center, open-label, single active arm intervention;Adult patients with severe COVID-19 pneumonia (as evaluated by CT scanning), hypoxia (PaO2:FiO2 ratio ≤ 300 mmHg), and systemic hyper-inflammation (increased C-reactive protein [CRP] ≥ 100 mg/mL and/or ferritin ≥ 900 μg/L, increased lactate dehydrogenase [LDH]) received a single intravenous dose of mavrilimumab added to standard of care;follow-up 28 days Main outcomes measure was time to clinical improvement (reduction ≥ 2 categories on the 7-point WHO clinical status scale, 1=discharge, 7=death);others included time to discharge from hospital;% of pts achieving a clinical improvement;survival;mechanical-ventilation free survival;time to fever resolution;CRP;PaO2:FiO2 ratio Results:A mavrilimumab group (n=13 COVID-19 patients, non-mechanically ventilated, median age 57 [IQR, 52-58], males 12 [92%], febrile 11 [85%];PaO2:FiO2 195 5[166 7–215 0]) was compared to a cohort of 26 contemporaneous patients with similar baseline characteristics Death occurred in 0% (n=0/13) of mavrilimumab recipients and 27% (n=7/26) of comparison-group patients (log rank p=0 046) during the 28-day follow-up 100% (n=13) of mavrilimumab recipients and 65% (n=17) of comparison-group patients achieved clinical improvement (p=0 018) at Day 28, with earlier improvement (median 8 0 [IQR, 5 0–11 0] days vs 18 5 [11 0–NE] days) (p0 001) in mavrilimumab recipients Fever had resolved in 91% (n=10/11 febrile patients) of mavrilimumab recipients by Day 14, compared to 61% (n=11/18 febrile) of patients in the comparison group (p=0 110);fever resolution was faster in mavrilimumab recipients versus controls (median 1 0 [IQR, 1 0–2 0] day vs 7 0 [3 0 - NE] days, respectively, p=0·009) Mavrilimumab was well tolerated in all patients Conclusion:Patients with severe COVID-19 pneumonia and systemic hyper-inflammation who received treatment with mavrilimumab had better clinical outcomes compared to patients receiving routine care Mavrilimumab was well-tolerated Randomized controlled trials are warranted to confirm our findings References:[1]Zhou F, Yu T, Du R, et al Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Lancet 2020;395:1054-62[2]Mehta P, McAuley DF, Brown M, et al HLH Across Speciality Collaboration, UK COVID-19: consider cytokine storm syndromes and immunosuppression Lancet 2020;395:1033-4Disclosure of Interests:Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Giulio Cavalli Speakers bureau: SOBI, Novartis, Pfizer, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Emanuel Della Torre: None declared, Piera Angelillo: None declared, Alessandro Tomelleri: None declared, nicola boffini: None declared, Stefano Tentori: None declared, Francesca Mette: None declared, Patrizia Rovere-Querini: None declared, Annalisa Ruggeri: None declared, Teresa D’Aliberti: None declared, Paolo Scarpelllini: None declared, Giovanni Landoni: None declared, Francesco De Cobelli: None declared, John F Paolini Shareholder of: Kiniksa, Employee of: Kiniksa, Alberto Zangrillo: None declared, Moreno Tresoldi: None declared, Bruce C Trapnell Consultant of: Kiniksa, Fabio Ciceri: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI