B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders

Abstract

Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and 55 lymphoma patients receiving their vaccines post B-cell depleting therapy (cohort 2). Half of the lymphoma patients in both cohorts achieved seropositivity compared to 100% of controls. In cohort 2, only 5% achieved an antibody response in the first year post B-cell depleting treatment, vs 88% treated >2 years prior. Also, 28% of patients with <50 B cells/µl achieved a serologic response vs 86% of patients with B-cell >50 B cells/µl. B-cell cytopenia is profound within the first year of exposure to B-cell depleting treatment, therefore an additional dose of vaccine within that timeframe is unlikely to raise antibody levels.

Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti–SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms

“…The other important point of our study is the insufficient antibody production in patients with BCL who received vaccination before the initiation of anti-CD20 MoAb treatment. Although this result was concordant with the result reported by Tanguay, 15 this was, at the same time, discordant with the findings of a previous study that reported that nAb remained for 4 months after vaccination in patients subsequently treated with B-cell depletion therapy. 9 The underlying reason for this discrepancy is currently unclear, although our study and the study by Tanguay et al included only 15 and 22 patients, respectively.…”

“…Nevertheless, there is consensus regarding the importance of the duration from completion of B-cell depletion therapy to vaccination within 6 to 12 months, which significantly impairs nAb production against the SARS-Cov-2 RNA vaccine. 10 , 12 , 13 , 15 In this regard, although data about the precise lymphocyte subset were unfortunately unavailable in our cohort, our study may preclude the necessity of precise blood cell/lymphocyte profiling, which is both labor-intensive and sometimes expensive, for predicting prompt nAb production after COVID-19 vaccination in a specific population of patients with BCL who were previously treated with B-cell depletion therapy.…”

“…In addition, we found that no other factors examined, including patient age and blood cell counts, were associated with seropositivity in our cohort, whereas previous studies suggested the relationship between white blood cell count; lymphocyte counts, including CD4-positive T cells and CD19-positive B cells; and the efficacy of COVID-19 vaccine in patients with lymphoma. 10 , 12 , 15 One of the conceivable reasons for these discrepancies might be the difference in the patient population analyzed, as the study by Narita included not only BCLs but also T-cell lymphomas and Hodgkin lymphoma, whereas the study by Perry included patients who were subjected to watch and wait without receiving anti-CD20 MoAb treatment. Tanguay et al pointed out that a peripheral B-cell count of <50/µL was a risk factor for poor antibody production after the COVID-19 vaccine, although this finding was not always related to prior anti-CD20 MoAb treatment.…”

Seroconversion to mRNA SARS-CoV-2 vaccines in patients with autoimmune cytopenias and bone marrow failures

“…Other strategies to improve seroconversion may be the choice of an alternative treatment if available (i.e. TPO-RA versus rituximab in ITP), vaccinating before B-cell depleting drugs, and allowing enough time for immune reconstitution in patients treated with B-cell depleting agents, as already suggested for lymphoproliferative disorders 20 , 21 . In this regard, Tanguay et al showed that rates of seroconversion raised to 88% if lymphoma patients had received B-cell depletion > 2 years prior to vaccine (versus 5% in those treated within 1 year before vaccine) 20 .…”

Strong Humoral but Not Cellular Immune Responses against SARS-CoV-2 in Individuals with Oncohematological Disease Who Were Treated with Rituximab before Receiving a Vaccine Booster

“…Consequently, there is major concern about the efficacy of COVID-19 vaccines in individuals treated with B-cell-depleting immunotherapy, as the experience with other vaccines has shown an impaired humoral response [ 1 , 2 , 3 ]. Recent studies confirmed that seroconversion in individuals on treatment with anti-CD20 after receiving two doses against COVID-19 is suboptimal compared with healthy donors (<10%) [ 45 , 46 ]. This percentage significantly increases after ceasing the treatment, from 17.5% in patients that ended anti-CD20 less than 6 months earlier [ 47 ] to higher results of 66–80% [ 28 , 45 , 47 , 48 ] 6–9 months since the last dose, which also concurs with the time of peripheral B-cell aplasia recovery.…”