Six-month antibody persistence after BNT162b2 mRNA COVID-19 vaccination in patients with chronic lymphocytic leukemia

Abstract

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to COVID-19 vaccination. Here, we evaluated SARS-CoV-2S antibody persistence at 6 months after a two-dose regimen of BNT162b2 COVID-19 vaccine in patients with CLL/small lymphocytic lymphoma (SLL) and healthy controls who had a documented initial response, 2-3 weeks after the second vaccine dose. In a total of 61 patients with CLL/SLL and 39 controls, antibodies were still detectable in 90.2% (n555) of the patients compared to 100% (n539) of the controls (adjusted odds ratio50.11, 95% CI 0.11-1.98; p50.079). Antibody titers decreased significantly overtime in both patients [from a median of 107.1 U/ mL (interquartile range (IQR), 4.6-672.6) to 67.5 U/mL (IQR, 8.0-203.6), p50.003] and controls [from a median of 983.2 U/mL (IQR, 610.9-1649.0) to 232.9 U/mL (IQR, 157.7-534.1), p,0.001]. Patients on active treatment (n514) had the lowest seropositivity rate (64.3%) and antibody titers [median52.8, (IQR, 0.5-17.6)]. Seronegativity occurred in 6 patients; 5 of them continued or initiated treatment during follow-up.In summary, the vast majority of patients with CLL/SLL who initially responded to COVID-19 vaccination remained seropositive at 6 months follow-up. However, antibody titers decreased significantly overtime and low titers or complete antibody loss were associated with active treatment. Patients with chronic lymphocytic leukemia (CLL) have increased risk for severe coronavirus disease 2019 (COVID-19) as well as mortality. 1,2 We and others have reported that patients with CLL/small lymphocytic lymphoma (SLL) have an impaired antibody response to COVID-19 vaccination. 3,4 Understanding the long-term persistence of SARS-CoV-2 antibodies after vaccination is highly important to ensure an appropriate vaccination strategy. COVID-19 messenger RNA (mRNA)-based vaccination in healthy subjects has been reported to elicit antibody response that persists for at least 6 months after the second vaccine dose 5 ; however, the durability of humoral response in patients with CLL/SLL is still unknown. Here, we report an updated analysis of our primary cohort that now focuses on antibody persistence after a 2-dose regimen of BNT162b2 COVID-19 vaccine in patients with CLL/SLL. This prospective study was conducted in the framework of the European Research Initiative on CLL. The study was approved by the institutional review board and is registered in ClinicalTrials.gov (no. NCT04746092). All subjects provided informed consent. Eligibility criteria for the study included diagnosis of CLL/SLL according to the International Workshop on Chronic Lymphocytic Leukemia criteria, 6 age 18 years or older, with no known history of SARS-CoV-2 infection. The study has also included healthy volunteers that served as a control group. Patients and healthy controls who participated in the primary cohort 3 and achieved a serologic response, 2 to 3 weeks after the second vaccine dose, were reevaluated for antibody persistence at 6 months after vaccination. Serum sampl...

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

“…In CLL patients who do respond to vaccination, 36 this remains intact for at least six months. However, among CLL patients who fail to respond to two vaccination doses, the response rates to third or more doses are likely to be low, and with low levels of anti‐S 37 .…”

“…In CLL patients who do respond to vaccination, 36 this remains intact for at least six months. However, among CLL patients who fail to respond to two vaccination doses, the response rates to third or more doses are likely to be low, and with low levels of anti-S. 37 Nevertheless, third and perhaps fourth vaccine doses are the easiest and most immediately available option and supported by our T-cell FluoroSpot data showing a functional T-cell anti-COVID-19 response in ~80% of patients.…”

Current perspectives regarding SARS‐CoV‐2 vaccination in chronic lymphocytic leukemia

“…Recent studies on SARS‐CoV‐2 vaccination in CLL have evaluated the persistence of SARS‐CoV‐2 antibodies after vaccination. 48 , 49 Tadmor and co‐workers. 48 found that the decline of SARS‐CoV‐2 antibody levels in CLL patients, assessed after a median time of 100 days after vaccination was no different from that of elderly healthy controls.…”

“…However, antibody titers declined dramatically with time, and active therapy was linked to a loss of response. 49 …”

mRNA COVID‐19 vaccines in patients with chronic lymphocytic leukemia: A systematic review and meta‐analysis

“…F I G U R E 1 Rate of seroconversion after SARS-CoV-2 mRNA vaccine on pooled meta-analysis in the general population of CLL patients (A), in patients treatment-naïve (B), in patients who had been given an anti-CD20 monoclonal antibody at any time before vaccination (C), patients vaccinated within 12 months from the last infusion of anti-CD20 antibody (D), patients on therapy with BTKi (E), and patients on therapy with venetoclax (F) Identifying subgroups of CLL patients with different responses to SARS-CoV-2 vaccination and antibodies persistence over the time is important to decide treatment strategies and developing studies aimed at improving response to vaccination. 20,21 Recent preliminary results indicate that a third dose ("booster") of SARS-CoV-2 mRNA vaccines induces seroconversion in 42% of the patients seronegative after the second vaccination dose. 17…”