COVID-19 in patients with Chronic Lymphocytic Leukemia treated with venetoclax: what is the role of anti-CD20 antibody?

Ongoing antileukemic treatment may worsen the immunological status of patients with chronic lymphocytc leukemia (CLL), possibly leading to worse outcomes of COVID-19.2-3 A recent meta-analysis showed a high case fatality rate in hospitalized patients with hematological malignancies4 and published reports indicated high rates also in CLL patients.5-9 Outcomes ameliorated with the introduction of new drugs against SARS-CoV-2, but a great reduction of the mortality rate was allowed by prophylaxis with the vaccines administration.7 Our study aimed to evaluate the impact of COVID-19 in patients with CLL treated with venetoclax, based on the data collected within a retrospective study conducted by the SEIFEM (Sorveglianza epidemiologica infezioni nelle emopatie) group. The retrospective multicenter study included 258 patients with CLL treated from January 2017 to December 2022 with venetoclax single agent until progression or toxicity (122 patients) or venetoclax plus anti-CD20 antibody as fixed duration therapy (136 patients, of whom 128 venetoclax plus rituximab and 8 venetoclax plus obinutuzumab). Median time on venetoclax was 20 months (range 1-68); patients previously exposed to venetoclax who withdrew treatment before the onset of the pandemic in February 2020 were excluded. In conformity to what previously reported in other settings of immunological treatment of hematological cancers,10 we have considered three different ERAs: the first period (ERA-1) spanned from the beginning of the COVID-19 pandemic until the time in which SARS-CoV-2 vaccination was available (February 2020 through February 2021), the second period (ERA-2) spanned from the beginning of SARS-CoV-2 vaccination until the time in which passive prophylactic measures with tixagevimab-cilgavimab became available (March 2021 through March 2022) and the third period (ERA-3) began with the initiation of passive prophylactic measures with tixagevimab-cilgavimab (from April 2022).