EARLY, BUT NOT LATE USE OF REMDESVIR AND CONVALESCENT PLASMA REDUCES MORTALITY OF COVID 19 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES - A STUDY OF KROHEM

ABSTRACT

Background: Patients with hematologic malignancies have a high risk of dying from COVID19 due to inability to mount humoral and cellular immune responses to the virus. Remdesvir is an inhibitor of viral RNA-polimerase. Some, but not all studies suggest it hastens recovery and reduces mortality in patients with COVID19. In a large randomized trial, convalescent plasma obtained from persons recovering from the infection was not proven to be useful in treatment of COVID19 in the general population, but other studies suggest it is useful in hematologic patients unable to produce antibodies against the virus. Recommendations on the use of these two drugs vary, some recommend its use only in severely immunocompromized individuals, some only in serious cases and some not at all. Reflecting these differences, the practice of using them varied between Croatian centers during the current pandemic. Aims: To analyze the effect of remdesvir and convalescent plasma on mortality in patients with hematologic malignancies by performing a matched-pair analysis. Methods: KroHem, the Croatian Cooperative Group for Hematologic Diseases, collected data on the outcome of patients with hematologic malignancies who became infected with SARS-COV2 while on concurrent systemic antineoplastic therapy during 2020 and 2021, before the appearance of the omicron strain. Patients treated with remdesvir and/or convalescent plasma were matched to those untreated according to age, disease type and antineoplastic therapy, factors found in our previous analyses to be related to outcome. Patients with Hodgkin lymphoma and myeloproliferative neoplasms were excluded, due to low risk of COVID19 mortality. Death during infection was considered as due to COVID19. Results: We identified 119 patients fulfilling the entry criteria. Three could not be matched, 2 with T-PLL treated with alemtuzumab and one with plasmablastic lymphoma and newly diagnosed HIV infection. All three died. In the remaining 116 patient pairs remdesvir significantly reduced the mortality 36 out of 106 treated patients died, in comparison to 54 untreated (p=0.0207, McNemar's test). The effect of plasma was not significant 26 of 73 treated patients died, in comparison to 33 untreated (p=0.2812). Therapy was substantially more effective in patients who received treatment within a week from symptom onset;11 of 58 patients treated with remdesvir died in comparison to 33 untreated (p<0.0001) and 8 out of 35 treated with plasma in comparison to 20 untreated (p=0.0095). Patients treated with remdesvir only had similar outcomes as those treated with remdesvir and plasma (15% vs. 19% respectively). (Figure Presented ) Summary/Conclusion: Our study suggests that patients with hematologic neoplasia, who are at a high risk of dying from COVID19, should receive treatment with remdesvir and convalescent plasma as soon as possible, resulting in a 2.5-3 times reduction in mortality. The effect of later treatment, if any, is less prominent.