ABSTRACT
Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/µL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.
Subject(s)
COVID-19 , Lymphoma, Non-Hodgkin , B-Lymphocytes , BNT162 Vaccine , COVID-19 Vaccines , Humans , Lymphoma, Non-Hodgkin/therapy , RNA, Messenger , SARS-CoV-2ABSTRACT
BACKGROUND: Herpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients. OBJECTIVES: To study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adults with haematological malignancy undergoing allo-HCT. INTERVENTIONS: Antiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent. METHODS: Random-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I2). The certainty of the evidence was appraised by GRADE. RESULTS: We included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7-0.99; 15 trials, I2 = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34-0.85; n = 15, I2 = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2-0.43; n = 13, I2 = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/- pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6-1.02; n = 8, I2 = 0%), CMV disease (RR 0.47, 95% CI 0.23-0.97; n = 9, I2 = 30%) and HSV disease (RR 0.41, 95% CI 0.24-0.67; n = 4, I2 = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events. CONCLUSIONS: Antiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.