Vaccination against COVID-19 may produce a weaker immune response in patients with some haematological malignancies, according to several new studies. With both multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL), antibody responses appear lower after vaccination than in the general population.

In one study, a total of 93 patients with MM at one UK centre were included. Most of the cohort (71%) were on therapy for MM at the time of vaccination, and 52% were in a complete response or very good partial response.

At a median of 33 days following the first vaccine dose (either the Pfizer/BioNTech or AstraZeneca jabs), only 56% tested positive for SARS-CoV-2 IgG antibodies. There was no difference between those who received the Pfizer and AstraZeneca vaccines.

Notably, being on any therapy at the time of vaccination was associated with a lower rate of positive antibody result; no specific treatment was associated with lower rates than others.

The researchers also analysed the cohort using the Total antibody assay, which incorporates IgG, IgM, and IgA levels; this yielded a positive result in 33% of those who otherwise tested negative.

“Our data suggest lower positive antibody rates in patients with active multiple myeloma, patients with immunoparesis, and patients on any treatment,” wrote authors led by Dr Sarah Bird, of the Institute of Cancer Research in London, in The Lancet Haematology. The authors said that they advised their patients to avoid vaccination on a day they were receiving anti-myeloma therapy, with the exception of immunomodulatory agents.

“Omission of therapy pre-vaccination and post-vaccination should be balanced against the risk of disease relapse, so this decision making will need to be individualised,” they wrote. “That at least 30% of patients did not have a positive antibody test after first vaccination is concerning, and it will be important to track this group closely, as non-responders could be left vulnerable to severe COVID-19 infection.”

In another study of 48 MM patients in Greece, the median antibody titre level was 20.6%, compared with 32.5% in a control group. The weaker response, the authors hypothesised in Blood, may be due to the effect of myeloma cells suppressing normal B-cell expansion and immunoglobulin production. The B-cell depleting activity of some myeloma treatments could also play a role.

Patients with CLL may have an even poorer response to vaccination. In a study of 167 patients in Israel, also published in Blood, only 39.5% had a positive antibody-mediated response to the vaccine. A group of age- and sex-matched controls, meanwhile, had a 100% response rate to vaccination.

The response was highest among CLL patients who had obtained clinical remission after treatment (79.2%), followed by those who were treatment-naive (55.2%). The worst rate was seen in those under treatment at the time of vaccination (16%).

“Even though response rates were not optimal, patients with CLL should still get the vaccine and, if appropriate, it may be better to do so before CLL treatment starts although the disease itself may affect the response,” said Dr Yair Herishanu, of Tel Aviv University.