ASSOCIATIONS BETWEEN CLINICAL FACTORS AND RECENT ANTICANCER THERAPIES IN PATIENTS WITH CANCER AND COVID-19

Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Petros Grivas and colleagues analyzed a cohort of patients with cancer and coronavirus disease 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.¹

BACKGROUND

The SARS-CoV-2 pandemic has resulted in at least 3,2 million deaths worldwide.^2,3 Patients with cancer may have increased risk for SARS-CoV-2 infection^4-6 and worse outcomes.^7-14 Estimates of 30-day mortality associated with COVID-19 for patients with cancer range from 13% to 33%,^7,8 compared with 0,5% to 2% in the general population.¹ It is essential to understand factors associated with a high risk of adverse outcomes to inform clinical decision making in patients with cancer.^2,15

The pandemic has substantially changed oncology practice in many deleterious ways, which may worsen cancer-related outcomes.^14,16 Clinicians have attempted to balance the risks and benefits of cancer therapy by developing consensus-based algorithms to assist decision making.^17-20 The data of this cohort study on COVID-19 and patients with cancer can support and inform providers regarding prognostic factors and risk stratification, and also significantly broaden our understanding in this important topic.

RESULTS

A total of 4,966 patients with COVID-19 who had a diagnosis of cancer in the past were included (median age 66 years, 51% female, 50% non-Hispanic white) of which 2872 (58%) were hospitalized and 695 (14%) died. Of all patients, 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Approximately 80% had solid tumors, 51% had cancer in remission, and 40% received anticancer therapy within 3 months of COVID-19 diagnosis.

Multivariable analysis revealed higher COVID-19 severity among patients older than 40 years, males, and non-Hispanic black and Hispanic patients compared with non-Hispanic white patients (see Table 1 for odds ratios and 95% confidence intervals). In addition, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, worse ECOG PS and hematological malignancy were associated with higher COVID-19 severity. Active and progressing cancer, recent active cytotoxic chemotherapy, and COVID-19-directed treatments were also associated with higher severity.

Among hospitalized patients, low or high absolute lymphocyte count, high absolute neutrophil count, low platelet count, abnormal creatinine, troponin, lactate dehydrogenase and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later.

Specific anticancer therapies (R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. Notably, noncytotoxic systemic anticancer therapies including immunotherapy, targeted therapy, and endocrine therapy were not associated with higher COVID-19 severity (see Table 2).

CLINICAL IMPLICATIONS: COMMENT OF KEVIN PUNIE, MD, PHD, MEDICAL ONCOLOGIST, UZ LEUVEN

These findings can guide novel translational research, clinical trial designs, and clinical decision making for patients with cancer and COVID-19.

Several observational studies have shown a clear increased risk of morbidity and mortality of COVID-19 in patients with prior or current cancer when compared with patients without cancer history. However, the initial reports did not give proper insights into the association between clinical factors, laboratory variables or recent anticancer therapies and the adverse prognostic effect of cancer on outcomes of COVID-19, which has resulted in uncertainty regarding the associated risks with treatment and the correct weight of the anticancer treatment itself in the delicate benefit/risk balance in oncology.

In this study, Grivas and colleagues describe the associations between clinical, laboratory and demographic variables, cancer setting, cancer treatment and the temporal relationship between anticancer treatment and COVID-19 diagnosis.

Some adverse prognostic factors for COVID-19 outcomes such as obesity, cardiovascular or pulmonary comorbidities, worse ECOG performance status and hematological malignancies were clearly confirmed in this study. Additionally, several laboratory values associated with worse outcomes were identified in the oncological population. The most interesting findings were that within the patients with a cancer history, it were mainly those with active and progressing cancer and those who received active chemotherapy who experienced more severe COVID-19. Also some specific cytotoxic containing anticancer regimens were associated with worse outcomes and higher mortality in hospitalized patients, while there was no such adverse effect of non-cytotoxic systemic anticancer treatments. In the discussion with our patients, these are important findings that can help us in differentiating those patients who effectively have an increased risk of more severe  COVID-19 from those who do not belong to these higher risk categories and who are not at increased risk for severe COVID-19. When appropriate, we can incorporate this information in the benefit/risk balance  discussions with our patients, while on the other hand, we can rely on these data to reassure the latter category of patients.

References

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