A third of patients with the most common type of leukaemia fail to generate any measurable antibody response following two doses of COVID-19 vaccination.
Largest study of its kind
The largest study of its kind, the research identified a number of important new findings.
Researchers say these findings will be crucial to shaping future management and public health policy for patients with this type of blood cancer who are immunosuppressed and at an increased clinical risk from SARS-CoV-2 infection.
The study in numbers
500 patients with chronic lymphocytic leukaemia, the most common leukaemia in adults, were recruited to the study.
41% had received two doses of the Pfizer BioNTech vaccine, whilst 59% had received two doses of the Oxford AstraZeneca vaccine.
Average age 67
The average age of participants was 67 and 53% of the cohort was male.
Their antibody response to double COVID-19 vaccination was compared to that of 93 age-matched healthy ‘controls’.
Antibody response on 67% of leukaemia patients
Blood samples were obtained from all study participants between two to three weeks following their second vaccination, and again up to 30 weeks later.
Antibody responses were seen in 67% (336) of the leukaemia patients, compared to 100% (93) of age-matched controls.
Antibody level 3.7 times lower
In those with leukaemia who did generate an antibody response, the average antibody level was 3.7 times lower in magnitude and only just over a quarter (27%) of that seen in the healthy controls.
94 serum samples
Using serum samples of 94 of the leukaemia patients, and 94 healthy controls, the team also analysed their ability to neutralise live SARS-CoV-2 infection in the laboratory using:
In the healthy cohort, average neutralisation of live Wuhan and Delta virus was 96% and 84% respectively.
However, in the leukaemia patients, neutralisation of Wuhan virus was only 62% and even lower at 14% in the Delta variant.
Dr Helen Parry, a National Institute for Health Research (NIHR) academic clinical lecturer at the University of Birmingham, said:
Antibody titers 21-times higher
Meanwhile, antibody titers in leukaemia patients who had previously been infected with COVID-19 were 21-times higher than those seen in patients without previous infection.
This reveals a strong immunological ‘priming’ after natural infection.
The leukaemia patients without previous COVID-19 infection had equal antibody responses, no matter which of the two vaccines types they had been given.
Dr Graham McIlroy, clinical research fellow at the University of Birmingham, says:
The researchers also found that those with leukaemia most likely to fail to respond to COVID-19 vaccination are:
The scientists also analysed how antibody responses differed depending on the stage and treatment of the disease.
Those who have never been treated but are under active monitoring had the highest antibody response rates, with 79% showing a positive response.
The antibody response rate was lowest in patients who were actively being treated (43%).
While markedly higher rates of antibody response (56%) were seen in patients who had completed anti-CD20 therapy, a widely used treatment, more than 12 months prior to their second vaccine.
This compares to rates of 24% in those whose CD20 therapy ended less than 12 months prior to double vaccination.
Further protection needed
Paul Moss, Professor of Haematology at the University of Birmingham and principal investigator of the UK Coronavirus Immunology Consortium (UK-CIC), concluded:
Further protection needed
The research, published as a pre-print and therefore yet to be peer reviewed, was funded by the National Core Studies Immunity programme which is funded by UK Research and Innovation (UKRI).
Dr Jonathan Pearce, Director of the COVID-19 Response at the Medical Research Council (MRC), which is part of UKRI and co-funded the study, said: