Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma

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.

How to Provide the Needed Protection from COVID-19 to Patients with Hematologic Malignancies

“…We reviewed the literature to gather information on the seroconversion rates after receiving a COVID-19 vaccine in patients with hematologic malignancies. We selected 18 series that provided anti-SARS-CoV-2 spike protein IgG seroconversion rates after full COVID-19 vaccination detailed by hematologic malignancy diagnosis, with at least 20 patients per group (Figure 1 and Supplemental Table 1) (2,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The literature review also included six additional series that are not included in Figure 1, three due to sampling of serum antibodies before achieving full vaccination as evidenced by lower seroconversions in the healthy control group compared to the rest of the series (20,21), and three that did not provide breakdown of the data according to different histological diagnoses (22,23).…”

“…Important variables related to the hematologic malignancy, including being on active therapy, the type of therapy, being on watchful waiting before therapy, or having completed therapy, varied among the series and diagnoses. As a comparison, we provide the rates of seroconversion of healthy subjects from the series that included concomitant testing, which in some cases were age-matched controls (4,6,10,12,13,15,17,19,24). The combined healthy subjects group adds to 729 individuals, with seroconversion rates between 98-100% (Figure 1 and Supplemental Table 1), suggesting that these series adequately tested for anti-SARS-CoV-2 spike protein seroconversion at the time that healthy subjects would have responded to the vaccine.…”

“…Patients with chronic lymphocytic leukemia (CLL) have a particularly low rate of seroconversion after COVID-19 vaccination, ranging from 39% to 71% in the reported series (2,(5)(6)(7)(8)(9). A similarly low rate of seroconversion is evident in series reporting on patients with non-Hodgkin lymphoma (NHL), ranging from 42% to 75% (2,4,8,13,14,(16)(17)(18)(19)24). One series reported on patients with Waldenstrom macroglobulinemia (WM) with a 74% seroconversion rate (2).…”

Impact of anti-CD20 monoclonal antibodies on serologic response to BNT162b2 vaccine in B-cell Non-Hodgkin’s lymphomas

“…Multiple myeloma patients on anti-CD38 antibody therapy also respond partially and weakly [ 3 ]. The first observations on immunogenicity of anti-SARS-CoV-2 vaccines in patients with B-cell Non-Hodgkin’s Lymphoma (B-NHL) indicate that humoral response to BNT162b2 is deeply impaired in subjects undergoing anti-B cells monoclonal antibodies (moAbs) [ 4 – 6 ]. Such detrimental effect is not surprising, considering that a postponement to six months after therapy suspension has been suggested in patients exposed to anti-CD20 and anti-CD22 moAbs, anti-CD19 bispecific antibody and chimeric antigen receptor T-cells in vaccination settings other than COVID-19 [ 7 , 8 ].…”

Systemic COVID-19 vaccination also enhances the humoral immune response after SARS CoV-2 infection. An approach to criteria for COVID-19 re-immunization is needed. Do we need a third dose?

“…The same question can be asked about immunosuppression, people with immunode ciency syndromes, post transplantation patients, or oncologic or dialysis patients. Many published papers prove the safety of BNT162b2 vaccination in dialysis patients 18 , patients after lymphoma therapy 19 , and the safety of a third dose in kidney transplant recipients 20 . In healthy individuals, partial seroprotection, a mean of approximately 53% (32-68%, con dence interval 95%), is reached 14 days after the rst dose of BNT162b2 vaccine.…”