Efficacy and safety of ultra-low dose inhaled melphalan in the treatment of hospitalized patients with COVID-19

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need of creating the optimal tactics of efficient and safe anti-inflammatory therapy. A new method of treatment of COVID-19 with inhalation of ultra-low (non-cytotoxic) doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma.The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage.Materials and methods. A prospective, open, controlled, blind for the central expert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients of the control group were selected by an independent expert retrospectively using the computer algorithm for selecting «close» patients based on the «case-control» principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning of inhalations in the melphalan group and from the corresponding day in the control group.Results. Inhalations of melphalan led to a significant improvement in the clinical condition of patients according to the WHO scale, decrease in the intensity of dyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group.Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage