Humoral response to mRNA anti-COVID-19 vaccines BNT162b2 and mRNA-1273 in patients with chronic lymphocytic leukemia

Abstract

Immunocompromised individuals such as patients with chronic lymphocytic leukemia (CLL) are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses in patients with CLL after the first, second, and third doses of the BNT162b2 or mRNA-1273 vaccines and after a single dose for patients with confirmed previous COVID-19. In all, 530 patients were included in the study. Patients received 2 doses at a 4-week interval and a third dose if they were seronegative after the second dose. Response rate was 27% after dose 1 and 52% after dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients receiving therapy, those receiving Bruton tyrosine kinase inhibitor alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients who received venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariable analysis identified age older than 65 years, ongoing CLL treatment, and gamma globulin ≤6 g/L as independent predictors of the absence of seroconversion. Post-dose 2 seronegative patients had a global response rate of 35% after dose 3. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

Figure 1.

Antibody response rates in patients with CLL after 2 doses of COVID-19 vaccine. (A) Response rates by treatment history. TN patients had a response rate of 72% (151 of 210), significantly higher than that of previously treated patients (60%; 78 of 130; P = .02) and patients receiving therapy (22%; 36 of 166; P < .001). (B) Response rates for patients receiving therapy (n = 166) by treatment type. Patients receiving venetoclax monotherapy had a significantly higher response rate (52%; 12 of 23) than patients who were treated with BTKi’s (22%; 23 of 104; P < .001). All patients treated with venetoclax plus anti-CD20 mAb’s (n = 19) and venetoclax plus BTKi’s (n = 6) were seronegative after the second dose of vaccine. *P < .01; **P < .001; ***P < .0001.

Figure 2.

Multivariable analysis of serologic response in patients with CLL. ORs for antibody response after double-dose vaccination in a multivariable logistic regression analysis. Data points represent the ORs and 95% CIs.