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Immunotherapy during the COVID-19 pandemic

2020; Medknow; Volume: 3; Issue: 5 Linguagem: Inglês

10.4103/crst.crst_129_20

2590-3233

Aju Mathew, VinayMathew Thomas,

COVID-19 and Mental Health

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unleashing its fury through the coronavirus disease (COVID-19). The challenges of cancer care, which were already enormous, have just become unimaginably more complex. There is chaos all around us. Amid this, doctors of various specialties and regions and their respective societies have begun to debate, discuss, and provide recommendations on caring for patients with cancer in the time of COVID-19. These recommendations are based on two factors: (1) we know from the Chinese experience that patients with cancer are at a higher risk for getting infected with SARS-CoV-2 and (2) patients with cancer who develop COVID-19 have a higher chance of suffering complications from the infection.[12] Therefore, it is imperative that we reduce the risk of infection among our patients with cancer. What then can be done? First, we have to reduce the number of times they come to a hospital or clinic for cancer care. Second, we have to prevent the risk of immunosuppression in our patients. There are a few things that we can do to ensure that these two requirements are fulfilled. Several of our patients are on immunotherapy using checkpoint inhibitors for the programmed cell death protein (PD-1) and or programmed death-ligand (PD-L1). In a retrospective study from China, of 28 patients with COVID-19 and cancer, two patients had received immunotherapy within 14 days of the infection (one of them got immunotherapy combined with chemotherapy).[3] Those who got anticancer therapy in proximity to being diagnosed with COVID-19 had a higher risk for more severe disease (hazard ratio 4.08; 95% confidence interval: 1.09–15.32; P = 0.037). Therefore, what factors should we consider before we treat a patient with immunotherapy? First, we have to carefully weigh the benefits of starting or continuing immunotherapy against the harm of being on it. If the benefit-to-harm ratio is not significant, like in gastric or hepatocellular carcinomas, immunotherapy becomes even more trivial in the setting of an active COVID-19 pandemic. Second, we need to consider whether these medications are used in an adjuvant, neoadjuvant, or palliative setting. Third, we may consider switching to a less-frequent schedule. There is emerging evidence that a 4-weekly or 6-weekly dose would not cause a decrease in the efficacy.[4] One benefit with such a strategy would be the reduced exposure of the patients to the clinic or hospital. Fourth, where chemotherapy is administered concomitantly with immunotherapy, such as in case of lung cancer and head-and-neck squamous cell carcinoma, we may consider dose reduction or addition of granulocyte-colony stimulating growth factors to prevent immunosuppression. We would like to raise two caveats to keep in mind when thinking about COVID-19 in patients who are on immunotherapy. First, we are concerned about the immune-related adverse effects involving the lung (pneumonitis) that could develop with checkpoint inhibitor therapy. Therefore, patients with new-onset cough or shortness of breath should be evaluated not just with a computed tomography (CT) scan but also with a proper workup for the SARS-CoV-2 infection using the reverse transcription polymerase chain reaction-based testing, at least twice. Although some authors consider a syndromic approach of influenza-like illness and classic CT scan appearance of ground-glass opacities as suggestive of COVID-19, we recommend that the diagnosis be made only after a confirmatory laboratory test.[567] The treatment of immune-related adverse effects is the immediate initiation of steroids, whereas immunosuppression is relatively contraindicated in the initial stages of COVID-19. Second, we are also concerned about the role of checkpoint inhibitor-related immunomodulation in the immune hyperstimulation-related severity of COVID-19. Bonomi et al. described a patient who was on long-term immunotherapy for advanced lung cancer and had a rather rapidly fatal disease course. Until we have more data from clinical trials, anecdotal observations like these should be discussed and disseminated.[8] It is heartening to know that tocilizumab, an anti-interleukin-6 antibody drug used in the management of rheumatoid arthritis and cytokine release syndrome associated with chimeric antigen receptor T-cell therapy, has an anti-inflammatory role in the hyperimmune stimulation-driven severe COVID-19.[9] In fact, a multinational phase III clinical trial of the drug in severe COVID-19 disease will soon begin recruiting patients (NCT04320615). Another key immunomodulatory therapeutic strategy would be using natural killer (NK) cells, which form a major immune barrier against viral infections. A chimeric antigen receptor-modified NK-cell therapy trial has already started recruiting patients in China (NCT04324996). As oncologists, we always harp on the necessity of using data from clinical trials in our clinical decision-making. Well, for now, we are completely in a data-free zone when it comes to the use of immunotherapy in times of the COVID-19 pandemic. As clichéd as it sounds, "shared decision-making" is most relevant in this context. Let us discuss with our patients and help them make a decision regarding their care. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.