CLL-461 Humoral Response to COVID-19 Vaccine: A Challenge in CLL

Chronic lymphocytic leukaemia (CLL) is associated with some degree of immune dysfunction as a result of the disease itself and/or treatment. COVID-19 has a major impact on patients with CLL who are at increased risk for severe disease and death. In this study, we aimed to understand the efficacy of anti-SARS-CoV-2 vaccines in patients with CLL. From January 2021, we collected data on 166 vaccinated patients with CLL followed at our site. Median age was 68 years (range 41-92); 43 (26%) were treatment-naïve (TN), 25 (15%) were previously treated, 95 (57%) were on active therapy, and 3 (2%) were experiencing relapse. Most patients received BNT162b2 (87%), followed by mRNA-1273 (4%) and ChAdOx1-S (3%); data is missing in 6%. Serology testing was performed with the SARS-CoV-2 S1/S2 IgG assay (Elecsys® Anti-SARS-CoV-2) 2 to 3 weeks after second and third vaccine doses and considered negative for antibody titers below 0.4 U/ml. Vaccine response was evaluated post-dose 2 in 119 patients and post-dose 3 in 74 patients. Post second dose, a higher seroconversion rate was observed in TN patients and those with sustained clinical response after therapy discontinuation (42% and 46% respectively) compared with actively treated patients (20.5%; [p=0.024; p=0.048]). Antibody response rate in patients receiving BTKi was considerably lower 19.7% (12/61). Three (42.9%) out of 7 patients who received venetoclax monotherapy seroconverted. None of the patients exposed to anti-CD20 antibodies (3/8 with targeted therapy, 2/8 with chemotherapy, 3/8 as single agent) <12 months before vaccination responded. Among patients actively treated who failed to achieve a humoral response after two-dose, 25.6% responded to the third dose of vaccine, although with a weak antibody level (median 8.64 U/ml, range 0.55-175). Overall, post third dose a higher median (IQR) antibody titer (127.9 U/mL; 0.55-2500) was observed compared to one post second dose (19.2 U/ml; 0.86-2500) in patients on therapy. Notably, all patients in clinical remission after treatment present titers above the upper limit of quantification (>2500 U/mL) post third dose. Conclusions: Humoral immune response to the COVID-19 vaccine is impaired in most patients with CLL and correlates with treatment status.