Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment

To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); <i>p</i> = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); <i>p</i> &lt; .001). No serious adverse events were documented. Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients. Haematological patients face an increased risk for severe COVID-19. Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients. Persistent viral replication is increased in immunocompromised patients. Plitidepsin does not lead to new serious adverse events in immunocompromised patients.