Post-COVID immunity in patients with solid tumor or hematological malignancies treated with SARS-CoV-2 monoclonal antibodies

Abstract

Purpose: SARS-CoV-2 monoclonal antibody (mAB) therapy has effectively treated severe COVID-19, although how this contributes to protective antiviral immunity in settings of malignancy is poorly defined.

Patients and methods: We evaluated the development of post-infection immunity in five patients with malignancies who received mAB therapy targeting spike protein for their PCR-confirmed SARS-CoV-2 infection in 2021, compared with non-mAB controls. Patients were identified from a larger study on oncology with a history or documented current infection with SARS-CoV-2. Subjects include two patients with lymphoma and CD20-depletion therapy, one with myeloma and two with solid tumor (stage IIA rectal adenocarcinoma and metastatic breast cancer). Cancer therapies and COVID vaccination history varied by patient. Blood samples (1-4 per patient) were collected 71-635 days post-mAB therapy. We employed clinical histories with comprehensive immunoprofiling analysis, including systems serology antibody isotyping and effector function, T-cell immunophenotyping for subset and memory cells, and sensitive blood viral RNA detection up to 2 years post-mAB therapy.

Results: B-cell deficiency was confirmed in 3/5 patients. All patients had detectable anti-spike and nucleoprotein antibody isotypes, effector functions, and neutralizing antibodies (which increased over time by subject) at similar levels to the control group. Virus-specific T-cell activation and phenotypes varied by time and patient. Spike-specific effector and memory CD8 + T-cells were significantly elevated in mAB subjects compared to the control group. SARS-CoV-2 viral RNA detection was also higher in mAB-treated patients. One patient on bortezomib therapy had unique alterations in these populations.

Conclusion: All mAB-treated patients with malignancies developed polyfunctional immunity humoral and T-cell immunity to SARS-CoV-2 even in the setting of B-cell deficiency. The evolution of this immunity, including new variant-specific antibodies, without secondary illnesses suggests that patients were protected from symptomatic re-infection, and mAB therapy did not blunt the development of host immunity. Future studies are warranted to better characterize immunologic memory over time with exposures to new viral variants, evaluate prolonged viral shedding and the continued use of appropriate mAB for infection in high-risk patients.

Keywords: SARS‐CoV‐2; hematological malignancies; memory immunity; monoclonal antibody therapy.