Patients with B Cell Malignancy That Lacked Immune Response to Sars-Covid-2 Vaccination Mount Antibody Response Following Actual Sars-Covid-2 Infection: Potential to Improve Vaccination Strategy

SARS-Covid-2 (SCoV-2) infection has caused significant morbidity and mortality in patients with hematologic malignancies. Use of barrier protection with masks, hand hygiene, vaccination series and preventative monoclonal antibodies are methods for risk reduction of contracting symptomatic SCoV-2 infection. In the general population, SCoV-2 vaccination has been an effective approach to preventing SCoV-2 infection. Vaccination has been demonstrated to induce antibody (Ab) responses reflecting acquired immunity. However, such responses in patients with suppressed immune system have often been inadequate. There remains a need for an improved understanding of vaccine efficacy.

We have used the Veterans Administration (VA) Hospital data to evaluate SCoV-2 Ab responses after vaccination. Upon screening the National VA Corporate Data Warehouse (CDW) database, we identified a series of Veterans that did not develop protective Ab despite being vaccinated with at least two doses of SCoV-2 vaccine. From this cohort, we report a subset of patients that later developed symptomatic SCoV-2 infection. We analyzed immune response in these patients post-SARS-Covid-2 infection.

We identified four patients with B cell malignancies who initially had no antibody response to vaccination. However, all mounted a protective Ab response following SCoV-2 infection. The details of their B cell malignancy, treatment history along with COVID directed therapies are shown in Table 1. Patient #4 had end stage renal disease and had been on hemodialysis, otherwise patients did not have concomitant immunosuppressive illnesses like HIV, diabetes or chronic infections.

Conclusion: We report an interesting group of patients who had no humoral immune response to SCoV-2 vaccination. However, a strong immune response was observed in these patients with B cell malignancies following actual viral infection. Our data highlights ability of these patients to initiate an immune response to infection while not responsive to the vaccination itself. The observed response to infection may indicate a variable ability for antigen processing and/or presentation after vaccination versus actual infection. It may also indicate adjuvant role played by various cytokines produced during infection to facilitate immune response. These data indicate need to further study the immune processes operative in these patients with B cell malignancy and this understanding may allow improved antigen selection and presentation to augment immune responses to newer vaccination.

Munshi:Legend: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda Oncology: Consultancy; GSK: Consultancy.