Response to COVID-19 vaccination in patients on cancer therapy:Analysis in a SARS-CoV-2-naïve population

Background: Cancer patients have increased morbidity and mortality from COVID-19, but may respond poorly to vaccination. The Evaluation of COVID-19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS-CoV-2 community-transmission setting, allows determination of vaccine response with minimal interference from infection. Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID-19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre-second vaccine dose and at 1, 3 (primary endpoint), and 6 months post-second dose. SARS-CoV-2 anti-spike-RBD (S-RBD) and anti-nucleocapsid IgG antibodies were measured. Results: Ninety-six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID-19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p =.12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose. Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS-CoV-2 infection amplifies S-RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID-naïve population in studying vaccine immunogenicity.</p

Considerations for cancer immunotherapy during the COVID-19 pandemic

Cancer immunotherapy during the COVID-19 pandemic presents management challenges related to immune-related toxicities, requiring careful patient selection

Medical Oncology Group of Australia position statement: COVID‐19 vaccination in patients with solid tumours

People with cancer are vulnerable to increased morbidity and mortality from the coronavirus disease 2019 (COVID-19). COVID-19 vaccination is key to protecting the population of people with cancer from adverse outcomes of SARS-CoV-2 infection. The Medical Oncology Group of Australia aimed to address the considerations around COVID-19 vaccination in people with cancer, in particular, safety and efficacy of vaccination. The assessment of patients with generalised allergic reaction to anti-cancer therapy containing vaccine components and practical implementation of vaccination of people on active anti-cancer therapy are also discussed

Folic Acid Prevents and Partially Reverses Glucocorticoid-Induced Hypertension in the Rat

Background: To investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH4) in any effect of folic acid by comparing the effect of BH4 with that of folic acid in Dex hypertension. Methods: Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg/kg/d) or Dex (10 μg/rat/d). Folic acid (0.04 g/L drinking) or BH4 (10 mg/kg/d intraperitoneally) was started before (prevention) and during (reversal) glucocorticoid treatment. Results: Saline, BH4, vehicle for BH4, or folic acid alone did not change systolic blood pressure (BP). Systolic BP was increased by ACTH and Dex. Folic acid, but not BH4, prevented the development of hypertension caused by ACTH and Dex treatment. The ACTH and Dex hypertension were partially reversed by folic acid. The BH4 increased plasma total biopterin concentrations. The Dex decreased plasma NOx concentrations but had no effect on plasma biopterin concentrations. The ACTH and Dex increased plasma F2-isoprostane concentrations and decreased serum homocysteine concentrations compared with control but had no effect on serum folate concentrations. Folic acid increased serum folate concentrations compared with control but had no effect on homocysteine concentrations. Conclusions: Folic acid prevented and partially reversed both ACTH and Dex hypertension in rats without modifying the increase in plasma F2-isoprostane concentrations. Given that BH4 failed to prevent ACTH or Dex hypertension, folic acid is unlikely to be acting through increased BH4 production. The precise mechanism for the BP-lowering effect of folic acid in this model of hypertension remains to be determined

Evaluation of liver enzyme elevations and hepatotoxicity in patients treated with checkpoint inhibitor immunotherapy.

Background and aimsImmune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management.MethodsPatients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed.ResultsOf 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145-324 for immunotoxicity, N = 103; M = 74, 95% CI 59-92 for other causes; ratio of means 0.34, 95% CI 0.19-0.60, p = ConclusionsLiver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure