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

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: 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.

Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19.

OBJECTIVES: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. DESIGN: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. RESULTS: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). CONCLUSION: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.