COVID-19 Vaccine Failure in Chronic Lymphocytic Leukemia and Monoclonal B-Lymphocytosis; Humoral and Cellular Immunity

Chronic lymphocytic leukemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-Lymphocytosis (MBL) patients also have immune impairment. We evaluated humoral and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion (pppppp1000AU/mL. In a representative subset of 32 CLL patients, 80% had normal T-cell responses by IFNγ and IL-2 FluoroSpot assay. Failed seroconversion occurred in 36.6%% of treatment-naive patients, 52.9% treatment-naive with reduced IgM, 78.1% on therapy, and 85.7% on ibrutinib. Vaccination failure is very common in CLL, including early-stage disease.6 Key Novel FindingsComparison CLL vs MBL vs normal-45% of CLL and 9.5% of MBL fail to seroconvert with 2 doses of COVID-19 vaccineNeutralization assay-SARS CoV-2 IgG levels COVID-19-specific T-cell function by FluoroSpot IFN-g and IL-2 productionIgG, A, M class and IgG subclass:correlations by univariate and multivariate analysis-IgM (OR 7.29 pCorrelation withtherapy– ICT, targeted therapies, and those on Ig replacementHigh risk of vaccination failure for all CLL, including early-stage disease, and MBLKey PointsCLL and MBL show significantly impaired anti-spike antibody, viral neutralization, with cellular immune response to COVID-19 vaccinationFailure to seroconvert is associated with low IgM, IgG2, IgG3, and recent therapy; many CLL and MBL patients remain COVID-19 vulnerable