Low seropositivity and suboptimal neutralisation rates in patients fully vaccinated against COVID‐19 with B‐cell malignancies

Abstract

Patients with haematological malignancies are at increased risk of severe disease and death from coronavirus disease 2019 . 1 Vaccination is essential to increase population immunity and decrease disease burden. The first COVID-19 vaccines were authorised in the UK after phase III trials, which showed that both the BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines were effective at preventing symptomatic disease and hospitalisation. 2,3 Whilst both vaccines have demonstrated robust immune responses in healthy volunteers, patients with haematological malignancies were excluded from clinical trials. Emerging data suggest such patients are less likely to mount a humoral immune response to COVID-19 vaccination, with those who have received Bruton tyrosine kinase inhibitors (BTKi) or cluster of differentiation (CD)20directed therapies for B-cell malignancies a particularly highrisk group. [4][5][6][7] We report interim results from 55 participants recruited to our ongoing COV-VACC study, exploring the immune response to COVID-19 vaccination in patients with B-cell malignancies (South Central Berkshire B Research Ethics Committee and UK Health Research Authority approval IRAS number: 294547). Patients on treatment or treated within the last 24 months for a B-cell malignancy and receiving either the BNT162b2 (Pfizer-BioNTech; n = 41) or ChA-dOx1 nCoV-19 (Oxford-AstraZeneca; n = 14) vaccines were recruited. The median (range) age of participants was 60 (27-82) years and 50% were receiving systemic anti-cancer therapy (SACT) at the time of vaccination (Fig 1A , B).Blood samples were taken before vaccination and 1 month after the first and second vaccine doses. At each time-point, a full blood count and enumeration of whole blood

Reasons and consequences of COVID‐19 vaccine failure in patients with chronic lymphocytic leukemia

“…The response to the vaccination itself is more complex than only the titer of antibody, e.g., the seropositivity after vaccination may not equal virus neutralization capability in patients with B cell malignancies. 41 In addition, the vaccine's T cell immune efficacy can be higher than serological efficacy in patients with hematologic malignancies. 42 …”

“…Time from the end of systemic therapy to vaccination plays a role in response to the vaccine since the effect of drugs maintains after the completed treatment. 38 , 41 It was not likely that patients treated with anti‐CD20 antibodies within the last 12 months would respond to COVID‐19 vaccination 35 , 38 , 64 (Table 2 ). It is consistent with earlier meta‐analysis findings; response to different vaccinates improves incrementally after anti‐CD20 therapy.…”

“…Since patients with CLL may be at a high risk of COVID‐19 infections, 6 including the time after complete vaccination, 35 , 38 , 41 , 60 , 64 they need to be adequately informed about the potential lack of efficacy. The vaccination status itself does not preclude immunity in the group of patients with CLL.…”

“…The third dose administrated two months after the second in solid organ transplant recipients improved immunogenicity and prevented SARS‐CoV‐2 infection. 74 , 77 Fox et al 41 suggested that such an approach would benefit patients with CLL if they have been vaccinated within six months of active therapy. Already in France, immunocompromised patients are eligible to receive the third dose of vaccine.…”

“…et al 41 showed that CD19, CD4, and CD56 counts were significantly associated with seropositivity after the vaccination in the cohort of patients with B cell malignancies, including CLL. Low antigens count and total blood lymphocytes were associated with low antispike protein antibody positivity.…”