SARS-CoV-2 vaccines are highly effective at preventing severe COVID-19 in the general population; however, the efficacy of these vaccines in patients with immune suppression remains under investigation. A recent study published in Blood Cancer Journal demonstrated that antibody responses following COVID-19 vaccination are reduced in patients with chronic lymphocytic leukemia (CLL) relative to participants without leukemia.
The findings raised questions regarding optimal vaccination policy for patients with CLL, such as booster vaccines, and the continued need for behavioral adjustments, such as physical distancing.
Study participants received the BNT162b2 vaccine (Pfizer-BioNTech) or ChAdOx1 nCoV-19 vaccine (Oxford-AstraZeneca), both of which incorporate the SARS-CoV-2 spike protein as the vaccine immunogen and have recommend dosages that include 2 doses. The investigators evaluated spike-specific antibody responses via blood samples following first and/or second COVID-19 vaccination in patients with CLL (N=299) and age-matched healthy control participants (N=93).
Among the patient cohort, the median age was 69 years (range, 43-96). The median time to sample collection was 43 days (IQR, 36-52 days; n=267) after the first dose and 18 days (IQR, 14-28; n=55) after the second dose.
After the first dose, spike-specific antibody responses were detectable in 34% of patients with CLL compared with 94% of control participants (P <.0001), and antibody titers were 104-fold lower in patients with CLL relative to the control participants (0.4 vs 41.6 U/ml, respectively; P <.0001).
After the second dose, spike-specific antibody responses were detectable in 75% of the patients with CLL compared with 100% of the control participants (n=59). The antibody titers were 74-fold lower in patients with CLL relative to the control participants (53 U/ml vs 3900 U/ml; P <.0001).
Among patients with CLL, multivariate analysis revealed that current treatment with Bruton’s tyrosine kinase inhibitors (odds ratio [OR], 0.05; 95% CI, 0.004-0.58; P=.016) or immunoglobulin A deficiency (OR, 9.1; 95% CI, 2-42; P=.005) were independently associated with failure to generate an antibody response after the second dose.
The study found no differences in antibody levels following the BNT162b2 or ChAdOx1 vaccines.
Limitations of the study included relatively few patients in remission from previous chemotherapy, patient self-reporting for infection history, lack of assessment for prior COVID-19 infection (nucleocapsid-specific antibody) in some samples, inability include current hematological parameters, and relatively few samples from patients who had received both vaccine doses.
“In conclusion, we show that antibody responses following COVID-19 vaccination are reduced in patients with CLL, with patients who are IgA-deficient or on BTKi therapy at particular risk for failure to develop a response,” the authors wrote. “It is now critical that the clinical efficacy of vaccination is determined in this patient group using data linkage from large population datasets and this assessment is underway in many countries.”
Parry H, McIlroy G, Bruton R, et al. Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia. Blood Cancer J. 2021;11(7):136. Published July 30, 2021. doi:10.1038/s41408-021-00528-x