CCC19 Updates Uncover High All-Cause Mortality in Patients With COVID-19 and Cancer Receiving Select Chemotherapies

Patients with cancer who have contracted COVID-19 trend towards having high disease severity and mortality, especially among those with select demographic and clinical characteristics, with certain chemotherapy regimens contributing towards a high all-cause mortality, according to an analysis conducted by the COVID-19 and Cancer Consortium (CCC19) that was published in Annals of Oncology.¹

Of the 4966 patients who were included in the research, 2072 had uncomplicated disease while 2894 presented with complications. Among patients with complicated disease, 1675 were admitted to the hospital without requiring intensive care unit (ICU) intervention or mechanical ventilation and did not die. Moreover, 232 patients were admitted to the ICU without the need for ventilation, 292 required mechanical ventilation, and 695 patients died within 30 days.

The majority of patients who passed away were older at a median age of 75 years, while patients with other outcomes had a median age between 61 and 69 years. Male patients appeared to have worse COVID-19 severity vs female patients, according to the greater proportion of patients who received mechanical ventilation or died.

“Our findings confirm those from an earlier study from CCC19 and other studies,” lead study author Petros Grivas, MD, PhD, and coinvestigators wrote in the publication. “In particular, older age and male sex have been identified as negative prognostic factors among patients with or without cancer, although our study is the first, to our knowledge, to demonstrate a nonlinear relationship between age and risk.”

In total, 1803 patients received anticancer therapy within 3 months of their COVID-19 diagnosis, 90% (n = 1626) of whom had extractable free-test drug exposure with 125 drugs and classes of drugs that reportedly used. The majority of exposures included a single drug or class of drug (53%; n = 856), while 22% (n = 357) of patients received a minimum 3-drug combination.

Therapies such as platinum etoposide; regimens comprising rituximab (Rituxan), cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP); and DNA methyltransferase inhibitor regimens were associated with the highest 30-day and overall all-cause mortality. Conversely, regimens such as anthracycline, cyclophosphamide, and a taxane; daratumumab (Darzalex), an immunomodulatory agent, and dexamethasone; and ovarian function suppression plus an aromatase inhibitor yielded the lowest observed mortality.

Patients with cancer who contracted COVID-19 have an estimated 30-day mortality associated with the virus ranging from 13% to 33% vs 0.5% to 2% in the general population.^2-5 Investigators theorize that a better understanding of specific risk factors associated with poor outcomes in patients with COVID-19 and cancer may be able to better inform clinical management.

The international CCC19 has been working to collect data on patients who have both cancer and COVID-19.⁶ Previous research from the consortium has identified older age, male sex, smoking status, poor performance status, comorbidities, hematologic malignancies, and active cancer as possibly being associated with more severe patient outcomes.^7-9 With the hypothesis that certain demographic and clinical factors, as well as laboratory measurements impact the severity of COVID-19 in patients with cancer forming the rationale for the research, investigators evaluated data from nearly 5000 patients with COVID-19 and cancer.

Data were collected and managed through REDCap software hosted at Vanderbilt University Medical Center, through which reports were collected from March 17, 2020 to November 18, 2020. The research included patients with laboratory-confirmed COVID-19 confirmed by polymerase chain reaction and/or serology.

Exclusion criteria included patients with noninvasive cancers such as non-melanoma skin cancer, in situ carcinoma with the exception of bladder cancer in situ, or precursor hematologic neoplasms. Additionally, reports with low-quality data or incomplete outcome ascertainment that resulted in unknown status of the primary outcome were excluded from the analysis.

In total, investigators noted that 6968 reports were evaluable in the REDCap database, of which 4966 were included in the analysis. At a median follow-up of 42 days, 58% of patients included in the analysis were hospitalized during their COVID-19 course. The median age of the entire patient population was 66 years (range, 56-76) and was 70 years (range, 60-79) in the hospitalization subgroup. Female and non-Hispanic White patients comprised half of all patients in each group, with non-Hispanic Black patients comprising 22% of the overall patient population and 24% of the hospitalization subgroup.

Additionally, investigators reported that approximately 80% of patients had solid tumors, 51% were in remission, and 40% had received an anticancer therapy within 3 months of their COVID-19 diagnosis. Over half of all patients (61%) had cancer that was present, active, or treated within the past year.

Additionally, the multivariable analysis identified a higher COVID-19 severity among certain subgroups, such as patients older than 40 years, males, and non-Hispanic Black and Hispanic patients, vs non-Hispanic White patients. Clinical factors such as obesity, cardiovascular and pulmonary comorbid conditions, renal disease, diabetes mellitus, poor ECOG performance status, and hematologic malignancies were also associated higher disease severity. Moreover, patients who had progressive cancer, recent active cytotoxic chemotherapy, and COVID-19–directed therapies were associated with a higher COVID-19 severity.

“Many characteristics associated with higher COVID-19 severity, including cytotoxic chemotherapy, were also associated with 30-day mortality,” the authors wrote. “Factors such as Hispanic ethnicity and cardiovascular comorbidities had a weaker association that was no longer statistically significant. COVID-19–directed treatments had a substantial attenuation of the association in the 30-day mortality analysis, although all retained statistical significance.”

Laboratory measurements were collected from the hospitalization cohort upon being diagnosed with COVID-19 and analyzed. It was found that factors such as high and low absolute lymphocyte count, high absolute neutrophils count, low platelets, and abnormal levels of creatinine, troponin, or lactate dehydrogenase were associated with higher disease severity and 30-day mortality. Moreover, abnormal C-reactive protein was associated with a higher COVID-19 severity.

“These findings can inform novel translational research, clinical trial designs, and clinical decision making for patients with cancer and COVID-19,” the authors concluded. “Future planned work from CCC19 includes further investigation into health care disparities, outcomes for specific cancer subtypes, and impact of particular anticancer therapies.”

References

1. Grivas P, Khaki AR, Wise-Draper TM, et al. Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium. Ann Oncol. Published March 18, 2021. doi:10.1016/j.annonc.2021.02.024
2. Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907-1918. doi:10.1016/S0140-6736(20)31187-9
3. Garassino MC, Whisenant JG, Huang LC, et al. COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study. Lancet Oncol. 2020;21(7):914-922. doi:10.1016/S1470-2045(20)30314-4
4. WHO coronavirus (COVID-19) dashboard. World Health Organization. Accessed April 20, 2021. https://bit.ly/3v3iUZK
5. Estimating mortality from COVID-19. World Health Organization. August 4, 2020. Accessed April 20, 2021. https://bit.ly/3nbqG0X
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7. Lee LY, Cazier JB, Angelis V, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet. 2020;395(10241):1919-1926. doi:10.1016/S0140-6736(20)31173-9
8. Pinato DJ, Zambelli A, Aguilar-Company J, et al. Clinical portrait of the SARS-CoV-2 epidemic in European patients with cancer. Can Discov. 2020;10:1465-1474. doi:10.1158/2159-8290.CD-20-0773
9. Bakouny Z, Hawley JE, Choueiri TK, et al. COVID-19 and Cancer: current challenges and perspectives. Cancer Cell. 2020;38(5):629-646. doi:10.1016/j.ccell.2020.09.018