Sars-Cov-2 Antibody Levels in Blood Cancer Patients after a Third Sars-Cov-2 "Booster" Vaccination - Observational Data from the LLS National Registry
Authors: Greenberger Lee M , Saltzman Larry A , Senefeld Jonathon W , Johnson Patrick W , DeGennaro Louis J , Nichols Gwen L 
Published: November 2021

Abstract
Immunosuppressed patients may be at high risk for breakthrough COVID-19 infection despite SARS-CoV-2 vaccination, due to an inadequate or negligible antibody response. Based on data from the Leukemia & Lymphoma Society (LLS) National Registry, 25% of patients with hematologic malignancies do not produce anti-Spike protein antibodies in response to mRNA vaccines, with B-cell malignancy patients at highest risk (Greenberger et al, 2021, Cancer Cell, on-line). While studies of T-cell immunity, antibody cocktails, and booster vaccinations are underway, some patients have elected to receive an additional "booster" vaccination after a full course of SARS-CoV-2 vaccination. The LLS National Registry (NCT04794387) has collected Patient Reported Outcomes and serology from 3300 patients with hematologic malignancies. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically.
As of July 2021, the Registry includes 24 patients who obtained a 3 rd vaccination after full vaccination with mRNA vaccines. Twenty of these patients were seronegative &gt;14 days post 2 nd vaccination (as measured by the Roche Elecsys assay). Four patients had low positive serology results. All patients were nucleocapsid antibody negative.
Patient ages ranged from 51-79 years. Eleven had chronic lymphocytic leukemia (CLL), 7 non-Hodgkin's lymphoma (NHL), 5 Waldenstrom's macroglobulinemia (WM), and 1 multiple myeloma (MM). Six patients were not currently on anti-B cell therapy, 11 had received anti-CD20 therapy (8 within the last 6 months), 6 had received Bruton's tyrosine kinase (BTK) inhibitors within the last 6 months, and 1 patient had recently received chemotherapy. The booster vaccinations were obtained between April and June 2021, 21 to 114 days after completing the initial vaccination series between January and April 2021. Serology was performed 12-61 days post-booster vaccination. Fifteen patients received a heterologous adenovirus vaccine. Four patients received a heterologous mRNA vaccine, 5 patients received a homologous mRNA vaccine. Descriptive results are shown on the following table.
All patients (4) who had some level of antibody response to the initial vaccines had an augmented antibody response after a booster (i.e. sero-enhanced). Patients who had prior anti-CD20 often failed to seroconvert after booster vaccination. Only 2 of 8 patients who received anti-CD20 antibody treatment in the 6 months prior to vaccination seroconverted after booster vaccination. Two out of 3 seronegative patients receiving anti-CD20 therapy in the last 2 years (but &gt; 6 months) seroconverted after the booster. One patient with follicular lymphoma who received anti-CD20 therapy in 2019 remained seronegative despite a prolonged duration without therapy. Of the 6 seronegative patients taking BTK inhibitors, 3 seroconverted after the booster. Two of the 3 remaining seronegative patients were taking concomitant anti-CD20 therapy. Of the 4 seronegative patients not currently taking anti-B cell therapy, 3 seroconverted while one patient who currently required intravenous immunoglobulin remained seronegative. A patient currently receiving chemotherapy also did not respond to a booster.
In this limited set of patients there was no evident pattern of antibody response amongst patients who received homologous versus heterologous vaccine nor between disease types. While anti-CD20 therapy appeared to reduce antibody response to booster vaccination, there was substantial heterogeneity. Although many patients with B-cell malignancies did not mount a robust response to full mRNA vaccine series, several patients demonstrated an antibody response to the booster vaccination.
Clinical trials are needed to further understand who can benefit from a booster strategy as well as define the safety of the approach. The LLS Registry includes collection of Electronic Health Records, which will allow us to more specifically evaluate timing and dosage of boosters, the influence of prior therapeutics, as well as health and safety outcomes to better guide patients and physicians through the COVID-19 pandemic.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.

OffLabel Disclosure:
Booster vaccination (after full vaccination) using BNT162b2, mRNA-1273, or Ad26.COV2.S