Multiple COVID-19 vaccine doses in CLL and MBL improve immune responses with progressive and high seroconversion

• Published in: Blood Vol. 140; no. 25; pp. 2709 - 2721
• Main Authors: Shen, Yandong, Freeman, Jane A., Holland, Juliette, Naidu, Kartik, Solterbeck, Ann, Van Bilsen, Nenna, Downe, Paul, Kerridge, Ian, Wallman, Lucinda, Akerman, Anouschka, Aggarwal, Anupriya, Milogiannakis, Vanessa, Martins Costa Gomes, Gabriela, Doyle, Chloe M., Sandgren, Kerrie J., Turville, Stuart, Cunningham, Anthony L., Mulligan, Stephen P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-12-2022; by The American Society of Hematology
• Subjects: Antibodies, Viral; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; Immunity; Immunoglobulin G; Immunoglobulin M; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Lymphocytosis; Regular; SARS-CoV-2; Seroconversion
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022017814

•Multiple doses result in high rates of seroconversion in CLL (94.2%) and MBL (100%), with progressively higher antispike antibody levels.•Neutralization against COVID-19 variants requires strong specific T-cell responses and higher antispike levels.
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Patients with chronic lymphocytic leukemia (CLL) or monoclonal B-lymphocytosis (MBL) have impaired response to COVID-19 vaccination. A total of 258 patients (215 with CLL and 43 with MBL) had antispike antibody levels evaluable for statistical analysis. The overall seroconversion rate in patients with CLL was 94.2% (antispike antibodies ≥50 AU/mL) and 100% in patients with MBL after multiple vaccine doses. After 3 doses (post-D3) in 167 patients with CLL, 73.7% were seropositive, 17.4% had antispike antibody levels between 50 and 999 AU/mL, and 56.3% had antispike antibody levels ≥1000 AU/mL, with a median rise from 144.6 to 1800.7 AU/mL. Of patients who were seronegative post-D2, 39.7% seroconverted post-D3. For those who then remained seronegative after their previous dose, seroconversion occurred in 40.6% post-D4, 46.2% post-D5, 16.7% post-D6, and 0% after D7 or D8. After seroconversion, most had a progressive increase in antispike antibody levels. Neutralization was associated with higher antispike antibody levels, more vaccine doses, and earlier severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants; neutralizing antibody against early clade D614G was detected in 65.3%, against Delta in 52.0%, and against Omicron in 36.5%. SARS-CoV-2–specific T-cell production of interferon γ and interleukin 2 occurred in 73.9% and 60.9%, respectively, of 23 patients tested. After multiple vaccine doses, by multivariate analysis, immunoglobulin M ≥0.53 g/L, immunoglobulin subclass G3 ≥0.22 g/L and absence of current CLL therapy were independent predictors of positive serological responses. Multiple sequential COVID-19 vaccination significantly increased seroconversion and antispike antibody levels in patients with CLL or MBL.
Patients with chronic lymphocytic leukemia (CLL) and monoclonal B-lymphocytosis (MBL) respond poorly to the COVID-19 vaccination. Shen et al report on the incremental increase in successful immunization with repeated vaccination in 258 patients with CLL and MBL. With repeated redosing of the vaccine up to 6 doses, overall seroconversion is achieved in 94% of patients with CLL and 100% of patients with MBL, with concurrent increases in antibody levels and T-cell responses.