Judith A. Smith, Pharm.D. BCOP, CPHQ, FCCP, FISOPP, FHOPA
While the number of COVID-19 omicron cases start to wane and the pandemic is fading into an endemic, cancer patients remain vulnerable to COVID-19. Due to the compromised immunity patients undergoing active treatment for cancer, it has been estimated that cancer patients have a two-fold increased risk of contracting COVID-19 compared to the general population.1 Cancer patients undergoing active chemotherapy as well as cancer survivors experience more severe symptoms with prolonged hospitalizations and overall poorer prognosis compared to non-cancer patients with COVID-19 infections.2 Since the emergency approval of the COVID-19 vaccine the CDC has recommended prioritization of moderately or severely immunocompromised patients to be vaccinated.3 This includes cancer patients, organ transplant patients, stem cell transplant patients, advanced or untreated HIV, or on high dose corticosteroids. Across the board, ASCO, NCCN and CDC all recommend cancer patients receive the primary series of the COVID-19 vaccine regardless of if patient is on active chemotherapy, clinical trial, radiotherapy, or surgery.3-6
The controversy surrounding the COVID-19 vaccine and its administration to cancer patients has been mainly on the timing of completing the vaccination series. Patients participating or considering enrollment in clinical trials should also be vaccinated with close consideration of timing based on the mechanism of action of the investigational agents and potential adverse effects to be sure investigators can differentiate between vaccine adverse effects and what might be attributed to the investigational agents.7 Table 1 presents a summary of key recommendations based on current literature. Cancer patients that receive the COVID-19 vaccination while undergoing active chemotherapy are recommended to receive a third primary dose of the COVID-19 vaccine at least 28 days after completion of the two-dose mRNA COVID-19 vaccine series to help improve immune response.3,4 This additional third dose as part of primary series is not same as the current booster dose of COVID-19 vaccine which is also recommended for all patients that have completed the primary COVID-19 vaccine. Since there is not clear evidence on measuring COVID-19 antibody titer levels, it is not recommended for deciding the need for a booster shot or not.
COVID-19 in Cancer Patients
The symptoms of dyspnea and expectoration have emerged to occur more commonly in cancer patients. Other covid-19 related symptoms common in the general population such as sore throat and coryza are less often reported from patients with cancer. While not readily available to evaluate in all laboratories, cancer patients have had higher pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-), interleukin (IL)-6, and IL-2R compared to non-cancer patients with COVID-19.8 Patients that present febrile neutropenia should undergo COVID-19 molecular diagnostic testing as part of the standard of care work of febrile neutropenia (FN).9 Initiation of empiric antibiotics as appropriate should not be delayed waiting for test results. However, NCCN recommends against initiating use of G-CSF in cancer patients with acute COVID-19 infections to avoid increasing inflammatory cytokines levels and pulmonary inflammation.4,9 In patients with FN, use of G-CSF should be delayed until COVID-19 infection is ruled out.
Treatment of COVID-19 in Cancer Patients
Since cancer patients in general have had worse prognosis after contracting COVID-19 compared to the non-cancer population. expedited treatment and management of symptoms is recommended for cancer patients.10 When selecting medications to manage COVID-19 infection providers need close consideration of potential drug-drug interactions with medications being used to treat the cancer. Initially it is recommended to hold cancer treatment until the patient has complete resolution of symptoms for more than 24 hours including fever without use of antipyretic medication.
Management of COVID-19 in cancer patients is similar to the non-cancer patient population including initiation of oxygen to help alleviate hypoxia associated with pulmonary inflammation, corticosteroids/anti- inflammatory agents to combat the cytokine storm, antiviral treatments such as remdesivir, and use of immune enhancement therapy may help.10 It is a reasonable option to consider use of monoclonal antibody therapy (mAb) to treat COVID-19 in patients undergoing chemotherapy with mild to moderate symptoms. It is a reasonable option to consider use of mAb to treat COVID-19 in patients undergoing chemotherapy with mild to moderate symptoms.
Monoclonal Antibody Infusions
There are several mAb now available in the United States to treat COVID-19. The combination of casirivimab- imdevimab (11/21/2020) and bamlanivimab-etesevimab (2/9/2021) received emergency use authorization (EUA) by the FDA..3,4 4 Bamlanivimab was authorized (11/9/2020), however, authorization waslater revoked secondary to emerging resistance with variant strains.5 5 Sotrovimab (5/26/2021) and tocilizumab (6/24/2021) later received EUA. Tocilizumab is approved for hospitalized patients with severe disease only. Monoclonal antibody therapy can have some adverse toxicities including: fever, shortness of breath, weakness, arrhythmia, confusion, nausea, vomiting, hyperglycemia, pneumonia and potential hypersensitivity reactions. Limited data is available regarding the use of mAb in patients with active cancer undergoing treatment. In a case series of 42 patients with active cancer who also received mAb for COVID-19 it was reported there were limited adverse effects associated with the mAb.11 Within this case series, half of patients were female, 83% received bamlanivimab and there was a 12% rate of hospitalization. Hospitalization was found to be associated with CAR-T therapy and older age. Only 1/5 of hospitalized patients had a solid tumor diagnosis.6 Another case series of 38 patients with active cancer also found no adverse events with receipt of mAb.12 Within this case series 73% were on active therapy, 47% had heme malignancy, 22 received casirivimab/ imdevimab and all others received bamlanivimab.
Re-initiating Treatment in Cancer Patients Recovering from COVID-19
After holding chemotherapy during acute COVID-19 infection, it is recommended by ASCO to hold treatment for 10 days and to ensure the patient is symptom free for at least 24 hours prior to re-initiating treatment. Viral shedding may occur for an extended period after symptoms resolve so re-testing for COVID-19 is not recommended as a requirement to re-initiating treatment. Patients that have not previously completed the COVID-19 mRNA vaccine series can be vaccinated at least 90 days and have resolution of symptoms.
TAKE HOME POINTS:
1) Cancer patients have significant increased risk of contracting COVID-19 and it is highly recommended patients complete COVID-19 vaccination. If vaccinated while undergoing active treatment, a third primary dose at least 28 days after completion of the two-shot vaccine series is recommended. 2) Cancer patients need to continue to follow recommended precautions including face mask protection and physical distancing even after vaccinated. 3) Cancer treatment should be held during acute COVID-19 infection for at least 10 days and complete resolution of symptoms for greater than 24 hours.
It can also be used at a system level to act as a benchmark, or to indicate how one hospital or clinic is doing in comparison to another hospital or unit, in terms of a total aggregated monthly or annual compassion scores for all their patients. In having this info a healthcare leader, can then go back and assess, support, and hopefully improve compassion at those particular care settings over time. So, we are excited about working with healthcare organizations and clinical settings in embedding the SCQ as a routine clinical and system measure, and then also holding organizations and healthcare teams accountable by reporting it and making it available to patients and families, helping them in determining, for example, which long term care home they would like to place their loved one in.
1) Al-shamshi HO, Alhazzani W, Alhuraui A, et al. A practical approach to the management of cancer patients during the novel coronavirus disease 2019 (COVID-19) pandemic: a international collaborative group. The Oncologist 2020;25:e936-e945. 2) Liu C, Zhao Y, Okwan-Duodu D, Basho R, Cui X. COVID-19 in cancer patients: risk, clinical features, and management. Cancer Biol Med 2020. Doi:10.20892/j.issn.2095-3941.2020.0289 3) CDC Guidelines COVID Vaccines for Moderately of Severely Immunocompromised People. COVID-19 Vaccines for Moderately or Severely Immunocompromised People | CDC 4) NCCN: Cancer and Covid-19 vaccination Version 5.0 01/04/2022 COVID-19 Resources (nccn.org) 5) ASCO Special report: A guide to cancer care delivery during COVID-19 pandemic ASCO SPECIAL REPORT: 6) NIH Covid19 treatment Guidelines: special populations. NIH and cancer COVID 19 section_93.pdf 7) Desai A, Gainor JF, Hegde A, et al. COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Nature Reviews-Clinical Oncology March 2021 https://doi.org/10.1038s41571-021- 00487-z . 8) Tian J, Miao X. Challenges and recommendations for cancer care in the COVID-19 pandemic. Cancer Biol Med 2020. Doi:10.20892/j.issn.2095-3941.2020.0300. 9) NIH Covid19 treatment Guidelines: special populations. NIH and cancer COVID 19 section_93.pdf 10) Liu C, Zhao Y, Okwan-Duodu D, Basho R, Cui X. COVID-19 in cancer patients: risk, clinical features, and management. Cancer Biol Med 202. Doi: 10.20892/j.issn.2095-3941.2020.2089 . 11) Puing AG, Ho S, Frankel P, et al. SARS-CoV-2 Specific Monoclonal Antibody for the Treatment of Mild-to- Moderate COVID-19 in Cancer Patients: A Single-center Experience. J Infect Dis. 2021. 12) Curgliano G, Banerjee S, Cervantes A, et al. Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus. Annals of Oncol 2020; 31(10):1320-1335.
Fredrick D. Ashbury, PhD
Chief Scientific Officer, VieCure Professor (Adj), Department of Oncology University of Calgary Professor (Adj), DLSPH, University of Toronto
Judith A. Smith, Pharm.D., BCOP, CPHQ, FCCP, FISOPP, FHOPA
Professor, Division of Gynecologic Oncology, Dept OB/Gyn & Repro Sci, McGovern Medical School, Senior Clinical Pharmacist & Pharmacy Scientist, VieCure