Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia

Herishanu, Yair; Avivi, Irit; Aharon, Anat; Shefer, Gabi; Levi, Shai; Bronstein, Yotam; Morales, Miguel; Ziv, Tomer; Shorer, Yamit; Scarfò, Lydia; Joffe, Erel; Perry, Chava; Ghia, Paolo

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study (NCT04746092) was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to BNT162b2 mRNA COVID-19 vaccine in patientswith CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured using Elecsys® Anti-SARS-CoV-2S assay after administration of the second dose. In a total of 167 patients with CLL the antibodyresponse rate was39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy controls, revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio=0.010, 95% CI 0.001-0.162; p<0.001). Response rate was highest in patients who obtained clinical remissionafter treatment (79.2%), followed by 55.2% in treatment-naïveand 16% only in patients under treatment at the time of vaccination. In patients treated with either BTK inhibitors or venetoclax± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%, respectively). None of the patients exposed to anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, females,lack of currently active treatment, IgG levels ≥550 mg/dL and IgM levels ≥40mg/dL. In conclusion,antibody-mediated response to BNT162b2 mRNA COVID-19 vaccine in patients with CLLis markedly impaired and affected by disease activity and treatment.