Clinical Outcomes in COVID-19 Patients Treated with Immunotherapy

Abstract

Introduction: The full impact of COVID-19 infections on patients with cancer who are actively being treated with chemotherapy or immune checkpoint inhibitors (ICIs) has not been fully defined. Our goal was to track clinical outcomes in this specific patient population. Methods: We performed a retrospective chart review of 121 patients (age > 18 years) at the University of Alabama at Birmingham from January 2020 to December 2021 with an advanced solid malignancy that were eligible to be treated with ICIs or on current therapy within 12 months of their COVID-19 diagnosis. Results: A total of 121 patients were examined in this study, and 61 (50.4%) received immunotherapy treatment within 12 months. One quarter of the patients on ICIs passed away, compared to 13% of the post-chemotherapy cohort. Patients who were vaccinated for COVID-19 had lower mortality compared to unvaccinated patients (X2 = 15.19, p < 0.001), and patients with lower ECOG (0.98) were associated with lower mortality compared to patients with worse functional status (0.98 vs. 1.52; t = 3.20; p < 0.01). Conclusions: COVID-19-related ICI mortality was higher compared to patients receiving chemotherapy. However, ICI cessation or delay is unwarranted as long there has been a risk−benefit assessment undertaken with the patient.

Keywords: COVID-19; cancer; immune checkpoint inhibitors; immunotherapy.

Figure 1

Mechanism of action of PD-1/PD-L1 and CTLA4 inhibitors. Antigen presentation occurs on the surfaces of antigen-presenting cells (APCs) via T-cell receptors (TCR) and major histocompatibility complex (MHC). There are stimulatory and inhibitory signals, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1). Some of the upregulators of T-cells and their cognate ligands are CD27-CD70 and CD28-B7. Inhibitory T-cell receptors and their ligands include LAG3-MHC, CTLA4-B7 and PD1-PDL1. CTLA-4 reduces signaling via its co-stimulatory receptor, CD28, by binding to CD80 and CD86 on APC. CTLA-4 sends an inhibitory signal to T-cells. A CTLA-4 inhibitor (ipilimumab) stops autoreactive T-cells. PD-1 binds to programmed death-ligand 1 (PD-L1), which results in cancer evasion from the immune system. Blockade of PD-1 (via pembrolizumab, nivolumab, cemiplimab or dostarlimab) or PD-L1 (via atezolizumab, durvalumab or avelumab) increases anti-tumor immune activity. The image used has been modified from a prior submission [11].

Figure 2

Clinical outcomes of COVID-19 in cancer patients. COVID-19 can cause functional decline, respiratory distress and immunosuppression, which increases risks of hospitalization, chemotherapy interruptions and overall mortality.

Figure 3

Admission unit of COVID-19-affected patients (n = 121). In total, 32 (53.0%) of the immunotherapy patients required hospitalization and 6 (11.0%) were admitted to the ICU. For the patients on chemotherapy, 34 (56.0%) required hospitalization and 3 (5.0%) needed specialized care in the ICU.