Several retrospective studies have examined whether patients with cancer who develop COVID-19 may be at risk of more severe viral disease if their therapy includes immune checkpoint inhibition. Although the data are not uniform, for now, halting or modifying cancer treatment decisions is unnecessary; meanwhile, vigilance with testing for COVID-19 in this population is recommended.
In an ongoing global pandemic, one question oncologists have been investigating is whether their patients—already vulnerable to COVID-19—may be at risk of more severe viral disease if their cancer therapy includes immune checkpoint inhibition (ICI). The emerging answer is that, at least for now, halting or modifying ICI-related treatment is unwarranted.
Rather, vigilance with SARS-CoV-2 testing is “what we suggest for patients who are on or about to start ICI,” said Jedd Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY. He coauthored two recent retrospective studies showing that “any signal we've observed that ICI may worsen COVID-19 outcomes is modest, to say the most.”
One set of findings was presented by Jia Luo, MD, at the American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer, held July 20–22. The analysis focused on patients with lung cancer, identifying 69 who were diagnosed with COVID-19 between March 12 and April 13 (Cancer Discov 2020;10:1121–8). Of these, 41 had received prior ICI, primarily PD-1 blockade.
“We wanted to see if there might be differences between recent or more remote exposure to ICI, in terms of impact on COVID-19 severity,” Luo said. As such, the 41 patients included those dosed within 6 months of a COVID-19 diagnosis and those who had started ICI within 3 months of developing it. Virus “severity” was defined by the following outcomes: hospitalization rate, the need for intensive care, and death. After adjusting for potentially confounding factors—chiefly smoking history—the investigators found no significant association between PD-1 blockade and an increased risk of severe COVID-19.
On the other hand, such a link was uncovered in a second, broader study of 423 patients with various cancers and COVID-19 (Nat Med 2020;26:1218–23). The researchers reported that two predictors for hospitalization and severe respiratory illness—defined as requiring supplementary oxygen or mechanical ventilation—were prior ICI and being older than 65. In subanalyses of lung cancer versus non–lung cancer cohorts, higher rates of hospitalization and respiratory illness were still observed in patients who received ICI, regardless of cancer type. However, metastatic disease, recent chemotherapy, or major surgery were not significant predictors.
Regarding the apparent lack of concurrence, Wolchok noted that “both studies are modest-size data sets with different endpoints and inherent heterogeneity.” Some patients were treated at MSKCC, others at affiliated hospitals, “so our access to information—all collected during a very high-intensity time period—was not the same.” That chemotherapy did not emerge as a predictor was “surprising,” he added, but “there are probably other studies that suggest the opposite.”
Indeed, at the AACR meeting, Leora Horn, MD, of Vanderbilt University in Nashville, TN, presented data from the global TERAVOLT consortium showing that chemotherapy—but not ICI or targeted drugs—was associated with an increased risk of COVID-19 mortality among patients with thoracic cancers. Meanwhile, Aljosja Rogiers, MD, of Melanoma Institute Australia in Sydney, reported that, in a multicenter analysis of 113 ICI-treated patients, the mortality rate from COVID-19, at 8%, was similar to what has been reported for the general cancer patient population (between 7.6% and 12%) during the pandemic.
Overall, “it would be challenging to put COVID-19 in a single immune category,” Wolchok observed. “There are hypotheses that ICI could improve T-cell responses to the virus; alternatively, pneumonitis—part of PD-1 blockade's toxicity spectrum—could be exacerbated in the same context. We need to respect the limitations of these early analyses, but they've produced many observations to be followed in larger studies.”
MSKCC plans to share its data on COVID-19 outcomes with the Parker Institute for Cancer Immunotherapy, Wolchok added, “so we can begin to harmonize some of what we find. If there are further [virus] hot spots or second waves, perhaps we'll be better prepared with uniform ways of querying patient outcomes, to reduce heterogeneity.” –Alissa Poh
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