People at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), including patients dealing with malignancies and patients on immunosuppressive anticancer therapies, need to be followed carefully as the pandemic continues. Challenges in continuing cancer management and patient monitoring are of concern given the importance of timing in cancer therapy. Alternative treatment decisions and priorities are also important considerations. The efficacy and safety of various cancer treatments in patients with COVID-19 are other important considerations. In this systematic review, we summarize the potential risks and benefits of cancer treatments applied to patients with COVID-19 and malignant tumors. Using the PubMed and Scopus databases, we reviewed studies involving cancer therapy and COVID-19 to address the recent discoveries and related challenges of cancer therapy in patients with COVID-19 and cancer.
CalabròLPetersSSoriaJ-C, et al. Challenges in lung cancer therapy during the COVID-19 pandemic. Lancet Respir Med2020; 8: 542–544.
2.
FoxTTroy-BarnesEKirkwoodA, et al. Clinical outcomes and risk factors for severe COVID-19 infection in patients with haematological disorders receiving chemo- or immunotherapy. Br J Hematol2020; 191: 194–206.
3.
von Lilienfeld-ToalMVehreschildJJCornelyO, et al. Frequently asked questions regarding SARS-CoV-2 in cancer patients: recommendations for clinicians caring for patients with malignant diseases. Leukemia2020; 34: 1487–1494.
4.
AlhalabiOSubbiahV. Managing cancer care during the COVID-19 pandemic and beyond. Trends Cancer2020; 6: 533–535.
5.
AlshamraniMAl HarbiAAlkhudairN, et al. Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations. J Oncol Pharm Pract2020; 26: 1429–1440.
6.
MasoudiSNematiAHFazliHR, et al. An increased level of aryl hydrocarbon receptor in patients with pancreatic cancer. Middle East J Dig Dis2019; 11: 38–44.
7.
SalunkeAANandyKPathakSK, et al. Impact of COVID -19 in cancer patients on severity of disease and fatal outcomes: a systematic review and meta-analysis. Diabetes Metab Syndr2020; 14: 1431–1437.
8.
LiangWGuanWChenR, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol2020; 21: 335–337.
9.
BonomiLGhilardiLArnoldiE, et al. A rapid fatal evolution of coronavirus disease-19 (COVID-19) in an advanced lung cancer patient with a long time response to nivolumab. J Thorac Oncol2020;15: e83–e85.
10.
GatfieldEMukeshMLooS. Adjuvant systemic anti-cancer therapy in early breast cancer during the COVID-19 pandemic: differences between clinicians and patients in perception of treatment risks and benefits. Clin Oncol2020; 32: e218.
11.
MaioMHamidOLarkinJ, et al. Immune checkpoint inhibitors for cancer therapy in the COVID-19 era. Clin Cancer Res2020; 26: 4201–4205.
12.
SchreiberRDOldLJSmythMJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science2011; 331: 1565–1570.
13.
MohamadkhaniAPourshamsAVitiJ, et al. Pancreatic cancer is associated with peripheral leukocyte oxidative DNA damage. Asian Pacific J Cancer Prev2017; 18: 1349.
14.
BiDWenLWuZ, et al. GABAergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer’s disease. Alzheimer Dement2020; 16: 1312–1329.
15.
ChamilosGLionakisMSKontoyiannisDP. Are all patients with cancer at heightened risk for severe coronavirus disease 2019 (COVID-19)?Clin Infect Dis2021; 72: 351–356.
16.
KattanJKattanCAssiT. Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection?Immunotherapy2020; 12: 351–354.
17.
CavalcantiIDLSoaresJCS. Impact of COVID-19 on cancer patients: a review. Asia-Pacific J Clin Oncol2021; 17: 186–192.
18.
DuBoisRN. COVID-19, cancer care and prevention. Cancer Prev Res2020; 13: 889–892.
19.
NahmSRembielakAPeachH, et al. Consensus guidelines for the management of melanoma during the COVID-19 pandemic: surgery, systemic anti-cancer therapy, radiotherapy and follow-up. Clin Oncol2021; 33: e54–e57.
PetersGJ. Novel developments in the use of antimetabolites. Nucleosides Nucleotides Nucleic Acids2014; 33: 358–374.
23.
SchirrmacherV. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol2019; 54: 407–419.
GhiringhelliFApetohL. The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy. Exp Rev Clin Immunol2014; 10: 19–30.
26.
DuarteMBOLealFArgentonJLP, et al. Outcomes of covid-19 patients under cytotoxic cancer chemotherapy in Brazil. Cancers2020; 12: 3490.
27.
WilliamsMLe CalvezKMiE, et al. Estimating the risks from COVID-19 infection in adult chemotherapy patients. MedRxiv2020.
28.
TianJYuanXXiaoJ, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncol2020; 21: 893–903.
29.
YangKShengYHuangC, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study. Lancet Oncol2020; 21: 904–913.
30.
ShamsSMansoorK. COVID-19 and self-care measures by chemotherapy patients. Asia-Pacific J Oncol Nurs2020; 7: 310.
31.
Al-ShamsiHOAlhazzaniWAlhuraijiA, et al. A practical approach to the management of cancer patients during the novel coronavirus disease 2019 (COVID-19) pandemic: an international collaborative group. Oncologist2020; 25: e936.
32.
JeeJFooteMBLumishM, et al. Chemotherapy and COVID-19 outcomes in patients with cancer. J Clin Oncol2020; 38: 3538–3546.
33.
LeeLYCazierJBStarkeyT, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet2020; 395: 1919–1926.
34.
KanjanapanYYipD. Considerations for cancer immunotherapy during the COVID-19 pandemic. Med J Aust2020; 213: 390–392.
35.
AkulaSMAbramsSLSteelmanLS, et al. Cancer therapy and treatments during COVID-19 era. Adv Biol Regul2020; 100739.
36.
HarrisTJDrakeCG. Primer on tumor immunology and cancer immunotherapy. J Immunother Cancer2013; 1: 1–9.
37.
SathyanarayananVNeelapuSS. Cancer immunotherapy: strategies for personalization and combinatorial approaches. Mol Oncol2015; 9: 2043–2053.
38.
OldhamRKDillmanRO. Monoclonal antibodies in cancer therapy: 25 years of progress. J Clin Oncol2008; 26: 1774–1777.
39.
ŞakalarÇİzgiKCanatanH. Kanser immün terapi ve monoklonal antikorlar. Fü Sağ Bil Tıp Derg2013; 27: 105–110.
40.
MayorMYangNStermanD, et al. Immunotherapy for non-small cell lung cancer: current concepts and clinical trials. Eur J Cardio-Thoracic Surg2015; 49: 1324–1333.
41.
PapaioannouNEBeniataOVVitsosP, et al. Harnessing the immune system to improve cancer therapy. Ann Transl Med2016; 4.
42.
AgarwalSJuneCH. Harnessing CAR T cell insights to develop treatments for hyperinflammatory responses in COVID-19 patients. Cancer Disc2020; 6.
43.
PleyerCAliMACohenJI, et al. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood2021; 137: 185–189.
44.
HouotRLevyRCartronG, et al. Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine?Eur J Cancer2020; 136: 4–6.
45.
BakerDRobertsCAKPryceG, et al. COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin Exp Immunol2020; 202: 149–161.
46.
YarzaRBoverMParedesD, et al. SARS-CoV-2 infection in cancer patients undergoing active treatment: analysis of clinical features and predictive factors for severe respiratory failure and death. Eur J Cancer2020; 135: 242–250.
47.
TerposENtanasis-StathopoulosIElalamyI, et al. Hematological findings and complications of COVID-19. Am J Hematol2020; 95: 834–847.
48.
JiaoXNawabOPatelT, et al. Recent advances targeting CCR5 for cancer and its role in immuno-oncology. Cancer Res2019; 79: 4801–4807.
49.
RichardsonPGriffinITuckerC, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet2020; 395: e30.
50.
StebbingJPhelanAGriffinI, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis2020; 20: 400–402.
51.
Velasco-VelázquezMJiaoXDe La FuenteM, et al. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res2012; 72: 3839–3850.
52.
LedermanMMPenn-NicholsonAChoM, et al. Biology of CCR5 and its role in HIV infection and treatment. JAMA2006; 296: 815–826.
53.
AsokanIRabadiaSVYangEH. The COVID-19 pandemic and its impact on the cardio-oncology population. Curr Oncol Rep2020; 22: 60.
54.
MarovichMMascolaJRCohenMS. Monoclonal antibodies for prevention and treatment of COVID-19. JAMA2020; 324: 131–132.
55.
PattersonBKSeethamrajuHDhodyK, et al. Disruption of the CCL5/RANTES-CCR5 pathway restores immune homeostasis and reduces plasma viral load in critical COVID-19. medRxiv2020.
56.
Study to evaluate the efficacy and safety of leronlimab for mild to moderate COVID-19. ClinicalTrials.gov. National Library of Medicine; NCT04343651.
57.
Study to evaluate the efficacy and safety of leronlimab for patients with severe or critical coronavirus disease 2019 (COVID-19). ClinicalTrials.gov. National Library of Medicine; NCT04347239.
58.
National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology: non-small cell lung cancer. National Comprehensive Cancer Network; 2020.
59.
SebbaA. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health System Pharm2008; 65: 1413–1418.
60.
IshibashiKKoguchiTMatsuokaK, et al. Interleukin-6 induces drug resistance in renal cell carcinoma. Fukushima J Med Sci2018; 64: 103–110.
61.
ZhaoLYangYLiW, et al. Nivolumab-induced cytokine-release syndrome in relapsed/refractory Hodgkin’s lymphoma: a case report and literature review. Immunotherapy2018; 10: 913–917.
Tocilizumab in COVID-19 pneumonia. ClinicalTrials.gov. National Library of Medicine; NCT04317092.
67.
HuizingaTWFleischmannRMJassonM, et al. Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis2014; 73: 1626–1634.
68.
KampanNCXiangSDMcNallyOM, et al. Immunotherapeutic Interleukin-6 or Interleukin-6 receptor blockade in cancer: challenges and opportunities. Curr Med Chem2018; 25: 4785–4806.
69.
Al-SalamaZT. Emapalumab: first global approval. Drugs2019; 79: 99–103.
70.
LounderDTBinQde MinC, et al. Treatment of refractory hemophagocytic lymphohistiocytosis with emapalumab despite severe concurrent infections. Blood Adv2019; 3: 47.
71.
MertensMSinghJA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol2009; 36: 1118–1125.
72.
AndréPDenisCSoulasC, et al. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell2018; 175: 1731–1743.
73.
HaanenJBCerundoloV. NKG2A, a new kid on the immune checkpoint block. Cell2018; 175: 1720–1722.
74.
ZhengMGaoYWangG, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol2020; 17: 533–535.
75.
ZappasodiRMerghoubTWolchokJD. Emerging concepts for immune checkpoint blockade-based combination therapies. Cancer Cell2018; 33: 581–598.
76.
ChristofiTBaritakiSFalzoneL, et al. Current perspectives in cancer immunotherapy. Cancers2019; 11: 1472.
77.
DarvinPToorSMNairVS, et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med2018; 50: 1–11.
78.
La-BeckNMNguyenDTLeAD, et al. Optimizing patient outcomes with PD-1/PD-L1 immune checkpoint inhibitors for the first-line treatment of advanced non–small cell lung cancer. Pharmacotherapy2020; 40: 239–255.
79.
PicchiHMateusCChouaidC, et al. Infectious complications associated with the use of immune checkpoint inhibitors in oncology: reactivation of tuberculosis after anti PD-1 treatment. Clin Microbiol Infect2018; 24: 216–218.
80.
Del CastilloMRomeroFAArgüelloE, et al. The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clin Infect Dis2016; 63: 1490–1493.
81.
MichotJBigenwaldCChampiatS, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer2016; 54: 139–148.
82.
YounesASantoroAShippM, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol2016; 17: 1283-94.
83.
TurgemanIWollnerMHassounG, et al. Severe complicated neutropenia in two patients with metastatic non-small-cell lung cancer treated with nivolumab. Anti-Cancer Drugs2017; 28: 811–814.
84.
TabchiSWengXBlaisN. Severe agranulocytosis in a patient with metastatic non-small-cell lung cancer treated with nivolumab. Lung Cancer2016; 99: 123–126.
85.
PetrelliFArditoRBorgonovoK, et al. Haematological toxicities with immunotherapy in patients with cancer: a systematic review and meta-analysis. Eur J Cancer2018; 103: 7–16.
86.
FinkelISternschussMWollnerM, et al. Immune-related neutropenia following treatment with immune checkpoint inhibitors. J Immunother2020; 43: 67–74.
87.
KhanMM. Immunopharmacology. Springer; 2016.
88.
BachanovaVBishopMRDahiP, et al. Chimeric antigen receptor T cell therapy during the COVID-19 pandemic. Biol Blood Marrow Transpl2020; 26: 1239–1246.
89.
TeacheyDTLaceySFShawPA, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov2016; 6: 664–679.
90.
AgarwalS, June CH. Harnessing CAR T-cell insights to develop treatments for hyperinflammatory responses in patients with COVID-19. Cancer Discov2020; 10: 775–778.
91.
ParryJHallPYoungJ. New horizons in systemic anti-cancer therapy in older people. Age Ageing2018; 47: 340–348.
CrolleyVEHannaDJoharatnam-HoganN, et al. COVID-19 in cancer patients on systemic anti-cancer therapies: outcomes from the CAPITOL (COVID-19 Cancer Patient Outcomes in North London) cohort study. Ther Adv Med Oncol2020; 12: 1758835920971147.
94.
SngCCWongYNSWuA, et al. Cancer history and systemic anti-cancer therapy independently predict COVID-19 mortality: a UK tertiary hospital experience. Front Oncol2020; 10: 2452.
ReyndersKIllidgeTSivaS, et al. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev2015; 41: 503–510.
97.
YilmazMTElmaliAYaziciG. Abscopal effect, from myth to reality: from radiation oncologists’ perspective. Cureus2019; 11: e3860.
98.
NguyenNPBaumertBGOboiteE, et al. Immunotherapy and radiotherapy for older cancer patients during the COVID-19 era: proposed paradigm by the International Geriatric Radiotherapy Group. Gerontology2021; 67: 1–7.
99.
AghiliMGhalehtakiRDarzikolaeeNM, et al. Radiotherapy and COVID-19: practical recommendations from Iran. Radiother Oncol2020; 149: 70–71.
100.
García-SuárezJDe La CruzJCedilloÁ, et al. Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study. J Hematol Oncol2020; 13: 1–12.
101.
ZhangLZhuFXieL, et al. Clinical characteristics of COVID-19–infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann Oncol2020; 31: 894–901.
102.
KudererNMChoueiriTKShahDP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet2020; 395: 1907–1918.
103.
YangKShengYHuangC, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study. Lancet Oncol2020; 21: 904–913.
104.
TianJYuanXXiaoJ, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncol2020; 21: 893–903.
105.
MehtaVGoelSKabarritiR, et al. Case fatality rate of cancer patients with COVID-19 in a New York hospital system. Cancer Discov2020; 10: 935–941.
106.
DaiMLiuDLiuM, et al. Patients with cancer appear more vulnerable to SARS-COV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov2020; 10: 783–791.
107.
LeeLYCazierJBStarkeyT, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet2020; 395: 1919–1926.
108.
RobilottiEVBabadyNEMeadPA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nat Med2020; 26: 1218–1223.
109.
GarassinoMCWhisenantJGHuangL-C, et al. COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study. Lancet Oncol2020; 21: 914–922.
