COVID-19 and Cancer: Special Considerations for Patients Receiving Immunotherapy and Immunosuppressive Cancer Therapies

Abstract

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell–depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.

Navigating Uncharted Waters: Could COVID-19 and/or Certain COVID-19 Vaccines Promote Malignancy?

“…In sum, despite the fact that many institutions [168,169] and authors [170,171] maintain that COVID-19 vaccines are safe and (partially) effective in patients with cancer, these claims are supported by limited data and recommendations are largely inferred from vaccine safety and effectiveness in the general population; performance of other vaccines in patients with cancer; and immune alterations inherent in current cancer treatments [170]. Given the converging evidence of temporal association and biological plausibility, the contribution of genetic COVID-19 vaccines to cancer progression and recurrence cannot be excluded at present and constitute a signal to augment pharmacovigilance.…”

Severe COVID-19: Drugs and Clinical Trials

“…In general, antiviral nucleoside analogues are of concern due to their possible mutagenic role in host cells. Molnupiravir is known to be transformed in plasma to its active ingredient β-d-N4-hydroxycytidine (NHC), which presents a risk of off-target mutagenesis; notably, Zhou et al have reported that ribonucleosidated NHC induces DNA mutagenesis in dividing cells in vitro [235,[250][251][252]. Therefore, the use of other antiviral options or monoclonal antibodies is recommended prior to its administration.…”

“…Nirmatrelvir/ritonavir is one of the most promising drugs for patients with severe COVID-19; although clinical trials conducted in patients with mild COVID-19 presented risk factors, it decreases progression to severe COVID-19 and increases viral clearance. However, nirmatrelvir/ritonavir may interact with treatments in cancer patients, as the inhibition of CYP450 by ritonavir increases plasma levels of the metabolites of cancer treatments, with their reduced excretion increasing their side-effects [252,308]. Their use is not recommended in patients with renal insufficiency (e.g., an eGFR of less than 30 mL/min) [309].…”

Fatal Outcome of COVID-19 Relapse in a Fully Vaccinated Patient with Non-Hodgkin Lymphoma Receiving Maintenance Therapy with the Anti-CD20 Monoclonal Antibody Obinutuzumab: A Case Report

“…The elderly and patients with comorbidities have shown a more severe course of infection [ 3 ]. In particular, a worse outcome has been described among oncologic patients [ 2 , 4 , 5 ], and several studies have demonstrated that male sex, smoking status, and a diagnosis of hematologic malignancies or lung cancer are independently associated with disease severity and mortality in this population [ 4 ].…”

“…Patients with lymphoid cancers have been identified as being particularly at risk of inadequate antibody response to anti-SARS-CoV-2 vaccines [ 8 ], particularly those with non-Hodgkin lymphoma (NHL) receiving B cell-depleting agents [ 9 ]. Indeed, the impact of different antineoplastic therapies is largely variable; for example, immune check point inhibitors are not associated with a higher mortality risk in COVID-19 patients, unlike CAR T-cell therapies and anti-CD20 monoclonal antibodies [ 4 ].…”