ABSTRACT
Purpose: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. Methods: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. Results: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. Conclusions: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.
Subject(s)
Neoplasms , Lung Neoplasms , Carcinoma, Non-Small-Cell LungABSTRACT
Background Phase I/II clinical trials have explored whole-lung low-dose radiotherapy (LD-RT) as a potential treatment for patients with COVID-19-related acute respiratory distress syndrome (ARDS). Initial findings require reproduction. Concomitant LD-RT administration with existing therapies requires safety evaluation. Methods Patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared to controls blindly matched by age, comorbidity, and disease severity. Eligible patients were hospitalized, SARS-CoV-2 positive, had radiographic consolidations, and required supplemental oxygen. Endpoints included safety, clinical recovery, intubation, radiographic changes, and biomarker response. Findings 20 patients received whole-lung LD-RT between Jun 11 and Dec 7, 2020 and were compared to controls. Freedom from intubation improved from 68% in controls to 86% following LD-RT (p=0.09) as did C-reactive protein (CRP) (p=0.02) and creatine kinase (CK) (p<0.01) levels, consistent with prior report. Eighty percent of LD-RT patients experienced rapid decline in CRP within 3 days and were classified as LD-RT responders. Intubation-free survival (100% vs 66%, p=0.01) and oxygenation loads were lower in LD-RT responders compared to matched controls: 32% lower per individual (p=0.03) and 56% lower for the cohort (p=0.06). No patient whose CRP declined following LD-RT died or required intubation, whereas all LD-RT non-responders died. Observed reduction of prolonged recoveries and hospitalization times did not reach significance. Radiographic changes were equivalent. Interpretation A cohort of patients with COVID-19-related ARDS treated with LD-RT demonstrated superior freedom from intubation compared to matched controls, especially LD-RT responders (p=0.01). LD-RT appears safe to deliver with concurrent drugs. LD-RT lowered CRP and CK biomarkers. CRP response predicted favorable outcome. Optimal timing for LD-RT after oxygen dependence but before intubation may extinguish immunopathology prior to systemic spread. Confirmatory clinical trials are warranted. Clinical Trial Registration: NCT04366791 . Funding None