COVID-19 vaccination in patients with classic and variant hairy cell leukemia

COVID-19 spike antibodies in classic and variant hairy cell leukemia correlate with normal B-cells, which are reduced after anti-CD20 MAbs.

Since normal B-cells become reduced for several years after anti-CD20 Mabs, vaccines should be used before treatment if possible.

Patients with the B-cell malignancy hairy cell leukemia (HCL) and the poorer-prognosis variant HCLv often receive treatments including anti-CD20 monoclonal antibodies (Mabs) which kill normal B-cells, impairing humoral immunity. To study humoral immunity in HCL/HCLv, we measured COVID-19 antibodies after doses of COVID-19 vaccine in patients after different treatments. Patients with HCL (n=415) and HCLv (n=32) were studied. Total immunoglobulin levels were also determined. After the 2^nd COVID-19 vaccine dose, spike antibody level most strongly correlated with normal B-cell levels (r=0.365, p<0.0001), followed by CD4+ T-cell count (r=0.244, p=0.0002), and was less related to immunoglobulin G (IgG) level (r=0.101, p=0.14). Spike antibody levels also correlated with normal B-cells after the 3^rd to 5^th vaccine doses and with CD4+ T-cell count after the 3^rd dose. Normal B and CD4+ T-cell levels were interrelated. Normal B-cells were undetectable in 87% of 38 patients within 6 months after the last dose of anti-CD20 Mab and were lower than in patients at 6-12 months (p=0.0003), which in turn were lower than at 12-18 months (p=0.0002). Infection with COVID-19 became more common after use of the 3^rd vaccine dose; spike antibody levels were higher in patients with prior infection (positive vs negative nucleocapsid antibodies) (p<0.0001). Spike antibodies decreased with a median half-life of 53 days, faster after ibrutinib or anti-CD20 MAb. We conclude that decreased levels of normal B-cells in HCL/HCLv patients, due to disease and/or anti-CD20 therapy, are associated with lower COVID-19 vaccination efficiency and such patients may not respond well to vaccines. The associated studies are registered at www.clinicaltrials.gov as NCT01087333 (HCL/HCLv) and NCT04362865 (COVID-19).