According to the results of a systematic literature review, vaccine responsiveness was lower in patients who had received anti-CD20 therapy than in healthy or disease-control populations, regardless of the time that had elapsed from treatment, and for patients on active anti-CD20 therapy, regardless of the vaccine studied. The findings were reported in Blood Advances.

For the systematic literature review and metanalysis, the investigators searched (up to the week of January 4, 2021) major biomedical literature databases to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease.

The primary outcomes were seroprotection, seroconversion, and/or seroresponse rates for each type of vaccine reported among the identified studies. The meta-analysis was focused on the seroconversion in studies of the pandemic influenza vaccine (2009 H1N1) due to its similarity with the COVID-19 vaccine and standardized definitions for SP and seroconversion for the H1N1 vaccine.

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A total of 38 studies, including 19 studies of patients with hematologic malignancies, were identified, with 905 patients treated with anti-CD20 therapy. The studies included patients vaccinated against H1N1, seasonal influenza, tetanus, diphtheria, pertussis, Haemophilus influenzae B, hepatitis B, hepatitis A, polio, and pneumococcus.

Patients on active anti-CD20 therapy had poor responses to all types of vaccines, with seroconversion rates of 0% to 25%, but the response rates appeared to improve with the time elapsed since anti-CD20 therapy, with the best responses >12 months from therapy.

After 1 dose of the H1N1 vaccine, the pooled estimate for seroconversion in patient on active anti-CD20 therapy was 3% (95% CI, 0-9), with relative benefit ratios of 0.05 (95% CI, 0-0.73) and 0.22 (95% CI, 0.09-0.56) compared with healthy and disease-control group participants, respectively. Relative to both control groups, the seroconversion appeared to be lower for at least 6 months following anti-CD20 therapy; at 3-6 months after therapy, the relative benefit ratio was 0.50 (95% CI, 0.24-1.06) compared with healthy participants and 0.44 (95% CI, 0.23-0.84) compared with disease-control participants. For all vaccines studied, the response to vaccination in patients treated with anti-CD20 therapy improved with time; however, even >12 months after therapy, their responses were typically not equivalent to those of healthy participants.

“During the current pandemic, this argues for the need for rapid, real-world studies to guide clinical practice,” the authors wrote. “We need to quickly determine the seroconversion rate following COVID-19 vaccination, whether it can be improved upon with booster shots, and/or influenced via the timing of vaccination relative to anti-CD20 therapy.”

They also emphasized the need “to continue stringent evidence-based infection prevention strategies such as infection control measures, physical distancing, and appropriate shielding for patients on anti-CD20 therapy.” They also recommended COVID-19 vaccination for patients receiving anti-CD20 therapy, stating that “even a muted response to vaccination is likely better than no response.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Vijenthira A, Gong I, Betschel SD, Cheung M, Hicks LK. Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients. Blood Adv. 2021;5(12):2624-2643. doi:10.1182/bloodadvances.2021004629