Sars-CoV2 Antibody Responses in Patients with Hematological Malignancies Following Anti-CD20 Therapy
Authors: Guerra Veronica A , Ocampo Marisol , Cusnir Mike 
Published: November 2021

Abstract
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased mortality in patients with hematological malignancies, with increase rates between 33-37%. Vaccination against SARS-CoV-2 have shown efficacy decreasing infection rates, with efficacy rates of 50-95%. However, the immunogenicity in immune-compromised patients, particularly those with prior exposure to anti-CD20 antibodies and duration of protective immunity, remains unknown. The current guidelines recommend vaccination for all patients receiving cancer therapy with a 3 months delay following hematological stem cell transplant and CAR-T cell therapy.
Methods: We performed a retrospective analysis of the efficacy of SARS-CoV-2 vaccination in patients with hematological malignancies following anti-CD20 therapy. Adult patients, 18 years and older, with frontline and relapsed hematological malignancies were included. We performed a chart review to obtain treatment responses and analyze the correlation between clinical, biological, and demographic characteristics and antibody titer responses. SARS-CoV-2 antibodies were measure by qualitative IgG antibody analysis, SARS-CoV-2 Semi-Quantitative total antibodies and SARS-CoV-2 IgG antibody spike. Comparative analysis of response with a control group of patients with hematological malignancies with no prior exposure to anti-CD20 therapy was performed.
Results: A total of 29 patients (pts) were included. Twenty-five pts (86%) were &gt;65 years, with a median age of 73 years (49-93). Most patients were female (52%) with a diagnosis of non-Hodgkin Lymphoma (NHL) (86%). Twenty-four (83%) had rituximab therapy, and six pts (21%) had received Obinutuzumab. Baseline characteristics are listed in Table 1. Seventeen pts had completed treatment by the time of vaccination (59%), included 16 pts (55%) without any anti-CD20 therapy in the last 12 months. Four pts (14%) had common variable immunodeficiency (CVID).
Most pts received the Pfizer vaccine (83%), while 6% were given the Moderna vaccine and 3% J&J vaccine. The median time from last anti-CD20 therapy and SARS-CoV-2 antibody testing was 13 months (0-156). SARS-CoV-2 antibodies following vaccination were assessed after a median of 1.6 months (range 0.2-5 months). Overall a total of 44 measurements were done with a median of 1 assessment per patient (range 1-3).
With a median follow-up of 1.6 months from completion of vaccination, the overall response rate was 35%, with response rates of 24% for recent anti-CD20 exposure (&lt; 12 months) vs. 44% for patients with no exposure in the last 12 months. Response rates are listed in Figure 1.Figure 2 compares antibody titers distribution among hematological malignancy pts with a history of anti-CD20 therapy vs. the control group. The median SARS COV2 IgG Spike titers were 0.9 for the anti-CD20 subgroup vs. 4.9 in the control group (P=0.02). Only two patients had sequential vaccination with Pfizer and Moderna vaccines; however, neither developed antibodies despite re-vaccination. We did not identify any pts with a production of late antibody titers among pts with prior anti-CD20 exposure.
Response rates were significantly decreased among pts with prior anti-CD20 exposure with ORR 35% vs. 65% for pts with hematological malignancies without anti-CD20 treatment (P=0.002)
We performed univariate analysis to determine the clinical factors associated with increased response rates. We found that decreased ALC counts were associated with decreased responses, while patients with no anti-CD20 therapy in the last 24 months were more likely to respond. There were no cases of COVID-19 infection following vaccination irrespective of titer responses.
Conclusions: While SARS-CoV-2 vaccination has shown to be effective and induces response rates from 50-95%, we found decreased response rates among immunocompromised cancer patients, particularly among those with anti-CD20 therapy. Responses were associated with absolute lymphocyte count and time from monoclonal therapy, with patients with normal levels and no therapy for over two years most likely to respond. However, despite low response rates, there were no cases of COVID-19 infection in our study. Further, follow-up is needed to determine the duration of response and persistence of antibodies.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.