Diminished Humoral and Cellular Responses to SARS-CoV-2 Vaccines in Patients with Chronic Lymphocytic Leukemia.

Prior publications have demonstrated low rates of seroconversion to the SARS-CoV-2 mRNA vaccines in patients with chronic lymphocytic leukemia (CLL). In this national collaboration of 11 cancer centers around the United States, we aimed to further characterize and understand the vaccine-induced immune response, including T-cell responses and the impact of CLL therapeutics (NCT04852822). Eligible patients were enrolled into two cohorts: 1) at the time of the initial vaccination and 2) at the time of booster vaccination. Serologic response rates (anti-S) from the 210 patients in the initial vaccination cohort and 117 in the booster vaccination cohort were 56% (95% CI, 50-63%) and 68% (95% CI, 60-77%), respectively. Compared to patients not on therapy, those receiving B-cell-directed therapy were less likely to seroconvert (OR 0.27, 95% CI 0.15-0.49). Persistence of response was seen at 6 months; anti-S titers increased with administration of booster vaccinations. In the initial vaccination cohort, positive correlations were seen between quantitative serologic response and CD4 T-cell response for the Wuhan variant and to a lesser degree, for the Omicron variant (Spearman P = 0.45 for Wuhan, P = 0.25 for Omicron). In the booster vaccination cohort, positive correlations were seen between serologic response and CD4 T-cell responses for both variants (P = 0.58 Wuhan, P = 0.57 Omicron) and to a lesser degree for CD8 T-cell responses (P = 0.33 Wuhan, P = 0.22 Omicron). While no deaths from COVID-19 were reported after booster vaccinations, patients should use caution as newer variants emerge and escape vaccine-induced immunity.