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

Abstract

Immunocompromised individuals such as chronic lymphocytic leukemia (CLL) patients are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate SARS-CoV-2-specific antibody responses in CLL patients, after the first, second and third doses of the BNT162b2 and mRNA-1273, and after a single dose for patients with confirmed prior COVID-19. Five hundred and thirty patients were included in the study. Patients received 2 doses at a 4-week interval, and a third dose if seronegative after the second dose. Response rate was 27% post-dose 1 and 52% post-dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients on therapy, patients on BTKi alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients on venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariate analysis identified as independent predictors of the absence of seroconversion: age >65 years, ongoing CLL treatment and gamma-globulins ≤6g/L. Post-dose 2 seronegative patients had a global post-dose 3 response rate of 35%. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

“…Patients with CLP have low antibody responses, especially those with CLL [ 63 ]. Several studies are consistent with response rate estimates of 35–75% in CLL [ 64 – 68 ] and 39–73% in NHL [ 66 , 68 , 69 ]. The main factors associated with poor responses were age over 70 years, decreased immunoglobulin levels, lymphopenia, anti-CD20 antibody administration within the last 6 to 12 months and use of Bruton Tyrosine Kinase inhibitors (BTKi) during the last 2 months.…”

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…Bagacean et al assessed the response to mRNA vaccine (71% BNT162b2, 14% mRNA-1273, 15% nonspecified mRNA) in 530 CLL patients. Median patient age was 71 (100). Fifty-two % of the patients achieved anti-spike binding IgG seroconversion.…”

Current perspectives regarding SARS‐CoV‐2 vaccination in chronic lymphocytic leukemia

“… 13 , 14 , 24 Furthermore, according to the results of three reports presented at the 2021 American Society Hematology meeting, the rate of seroconversion in CLL patients ranged from 52% to 61%. 25 , 26 , 27 …”

“…The results of pivotal studies conducted in the setting of patients with oncological and hematological disorders lended support for this approach. 27 , 34 , 35 In a small interventional phase one trial involving patients with solid tumors undergoing active anti‐cancer therapy, an increase in antibody responses with a median 3‐fold increase in virus‐neutralizing titers, was observed after the third dose of SARS CoV‐2 vaccine. 34 In this regard, the French Innovative Leukemia Organization (FILO) reported that administration of the third dose of the SARS‐CoV‐2 vaccine achieved effective seroconversion in 13 of 33 (42%) patients considered poor responders after the second dose of vaccine.…”