Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has led to dramatic changes in oncology practice. It is currently unknown whether programmed death 1 (PD-1) blockade therapy affects severity of illness from COVID-19 in patients with cancer. To address this uncertainty, we examined consecutive patients with lung cancers who were diagnosed with COVID-19 and examined severity on the basis of no or prior receipt of PD-1 blockade. Overall, the severity of COVID-19 in patients with lung cancer was high, including need for hospitalization in more than half of patients and death in nearly a quarter. Prior PD-1 blockade was, as expected, associated with smoking status. After adjustment for smoking status, PD-1 blockade exposure was not associated with increased risk of severity of COVID-19. PD-1 blockade does not appear to affect the severity of COVID-19 in patients with lung cancers. SIGNIFICANCE: A key question in oncology practice amidst the COVID-19 pandemic is whether PD-1 blockade therapy affects COVID-19 severity. Our analysis of patients with lung cancers supports the safety of PD-1 blockade treatment to achieve optimal cancer outcomes.This article is highlighted in the In This Issue feature, p. 1079.

Figure 1.

COVID-19 in patients with lung cancers. A, Daily cases and cumulative incidence of positive SARS-CoV-2 tests in patients with lung cancer. Date of positive SARS-CoV-2 test was unknown for 2 (3%) patients. B, Presenting signs and symptoms of COVID-19 infection in patients with known information. The most common presenting symptom was cough (77%) followed by dyspnea (73%), fever (70%), and need for supplemental oxygen (46%). Gastrointestinal symptoms were least common (22%). Error bars reflect 95% CI estimates of the population proportion. C, Baseline white blood cell count (median, 5.6 K/mcl; IQR, 4.1–8.2 K/mcl), absolute lymphocyte count (median, 0.7 K/mcl; IQR, 0.4–0.9 K/mcl), platelet count (median, 172 K/mcl; IQR, 134–220 K/mcl), aspartate aminotransferase (AST; median, 34 U/L; IQR, 22–53 U/L), alanine aminotransferase (ALT; median, 30 U/L; IQR, 21-39 U/L), and serum creatinine (median, 1.0 mg/dL; IQR, 0.8–1.5 mg/dL) in patients at the time of COVID-19 diagnosis. Dots represent individual values. Violin plots show the median and kernel density estimate distributions of each laboratory value. Dashed lines represent median, 25% percentile, and 75% percentile. Dotted lines and arrows in gray represent the normal range of the laboratory value. D, Exploded pie chart shows the rate of hospitalization (61%), and the status of patients requiring hospitalization. E, Patients were identified starting from the first case on March 12, 2020, through April 13, 2020, and followed until April 17, 2020. Median follow-up was 14 days (IQR, 7–23 days). Donut plot of patient status in regard to COVID-19 diagnosis at the time of last follow-up.

Figure 2.

Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers. A, Rate of hospitalization (left), ICU admission, need for intubation, and/or change to DNI status to avoid need for intensification of care (e.g., intubation; middle), or death (right) among patients with lung cancers with no prior PD-1 blockade exposure and those with prior PD-1 blockade exposure. Patients with no prior PD-1 blockade exposure are shown as all patients (n = 28), or limited to those with metastatic disease and/or ongoing active treatment for lung cancer (n = 19). Patients with prior PD-1 blockade exposure are shown as all patients (n = 40), those who had received the most recent dose of PD-1 blockade within 6 months of COVID-19 diagnosis (n = 30), those who had received the most recent dose of PD-1 within 6 weeks of COVID-19 diagnosis (n = 20), or those who began PD-1 blockade within 3 months of COVID-19 diagnosis (n = 13). Histogram represents the rate among patients with known status of the outcome displayed (known hospitalization status = 67/69, known ICU/intubation/DNI status = 65/69, and known died status = 67/69). Percent of cases are below each bar. Error bars represent 95% CIs. B, IL6 levels in patients with COVID-19, showing per-patient peak levels in no prior PD-1 blockade treated compared with prior PD-1 blockade treated. Dots represent individual values. Dashed lines represent median, 25% percentile, and 75% percentile. Violin plots show min–max ranges and kernel density estimate distributions of each group. Dotted line represents the upper limit of the normal range, 5 pg/mL. C, Forest plot showing unadjusted ORs for the impact of never receiving PD-1 blockade compared with any prior receipt of PD-1 blockade on severity outcomes associated with COVID-19 (hospitalization, ICU/intubation/DNI, and death). Unadjusted ORs for the impact of smoking history (<5 pack-years vs. ≥5 pack-years) on severity outcomes associated with COVID-19 (hospitalization, ICU/intubation/DNI, and death). ORs adjusted for smoking history, for the impact of never receiving PD-1 blockade compared with any prior receipt of PD-1 blockade on severity outcomes associated with COVID-19 (hospitalization, ICU/intubation/DNI, and death). ORs were calculated using univariate and multivariate logistic regression. Error bars represent 95% CIs. The x-axis is on a log scale.