Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients

Abstract

The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were searched up to 4 January 2021 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 (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (<3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 [95% CI, 0.24-1.06] compared with healthy and of 0.44 [95% CI, 0.23-0.84] compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.

Graphical abstract

Figure 1.

Flow diagram of studies assessed for inclusion.

Figure 2.

Risk benefit of SC to the pandemic influenza vaccine in anti-CD20–treated patients vs healthy controls. (A) On active therapy (<3 months from therapy). (B) Three to 6 months from therapy. (C) More than 12 months from therapy. Events, the number of patients with SC response to vaccination; Total, the total number of patients assessed for SC response to vaccination; Weight, the weighted contribution of each study to the meta-analysis.

Figure 3.

Risk ratios of SC to the pandemic influenza vaccine when treated with either 1 or 2 doses when comparing anti-CD20–treated patients to disease controls. (A) On active therapy (<3 months from therapy). (B) Three to 6 months from therapy. (C) Six to 12 months from therapy. (D) More than 12 months from therapy. Events, the number of patients with SC response to vaccination; Total, the total number of patients assessed for SC response to vaccination; Weight, the weighted contribution of each study to the meta-analysis.