ABSTRACT
Background: Inflammation and neutrophils play a central role in severe Covid-19 disease. In previous data, we showed that the FLARE score, combining both tumor and Covid-19-induced proinflammatory status (proinflamstatus), predicts early mortality in cancer patients (pts) with Covid-19 infection. We aimed to assess the impact of this score in a larger cohort and characterize the immunophenotype (IF) of circulating neutrophils. Methods: Multicenter retrospective cohort (RC) of pts with cancer and Covid-19 infection across 14 international centers. Circulating inflammatory markers were collected at two timepoints: baseline (-15 to -45d before Covid-19 diagnosis) and Covid-19 diagnosis. Tumor-induced proinflam-status was defined by high dNLR (neutrophils/(leucocytes-neutrophils)> 3) at baseline. Covid-19-induced proinflam-status was defined by +100% increase of dNLR between both timepoints. We built the FLARE score combining both Tumor and Infection-induced inflammation: T+/I+ (poor), if both proinflam-status;T+/I- (T-only), if inflammation only due to tumor;T-/I+ (I-only), if inflammation only due to Covid;T-/I- (favorable), if no proinflam-status. The IF of circulating neutrophils by flow cytometry was determined in a unicenter prospective cohort (PC) of pts with cancer during Covid-19 infection and in healthy volunteers (HV). Primary endpoint was 30-day mortality. Results: 524 pts were enrolled in the RC with a median follow- up of 84d (95%CI 78-90). Median age was 69 (range 35-98), 52% were male and 78% had baseline PS <1.Thoracic cancers were the most common (26%). 70% had active disease, 51% advanced stage and 57% were under systemic therapy. dNLR was high in 25% at baseline vs 55% at Covid-19 diagnosis. The median dNLR increase between both timepoints was +70% (IQR: 0-349%);42% had +100% increase of dNLR. Pts distribution and mortality across FLARE groups is resumed in the Table. Overall mortality rate was 26%. In multivariate analysis, including gender, stage and PS, the FLARE poor group was independently associated with 30-day mortality [OR 5.27;1.37-20.3]. 44 pts were enrolled in the PC. Median circulating neutrophils were higher in pts with cancer (n=10, 56.7% [IQR: 39-78.4%]) vs HV (n=6, 35.8% [IQR: 25.6-21%]), and particularly higher in pts with cancer and severe Covid-19 infection (n=7, 88.6% [IQR: 80.9-94%] (p=0.003). A more comprehensive characterization of the IF of circulating neutrophils, including Lox1/CD62/CD64, will be presented at ASCO. Conclusions: The FLARE score, combining tumor and Covid-19-induced proinflam-status, can identify the population at higher risk for mortality. A better characterization of circulating neutrophils may help improve the prediction of Covid-19 outcomes in pts with cancer. (Table Presented).
ABSTRACT
Background: The impact of coronavirus disease 2019 (COVID-19) on cancer patients is still unknown. We aimed to describe the clinical characteristics and 28-day mortality among patients with solid cancers (SC) and COVID-19. Methods: This single-center retrospective study included all adult patients with SC and RT-PCR confirmed COVID-19 between March 12, 2020 and April 30, 2020. Both oncological and COVID-19-related clinical data were collected. COVID-19 severity was defined according to Chinese CDC criteria. In-hospital and 28-day mortality were estimated. Multivariate analysis was adjusted for age, sex and COVID-19 severity. Results: We included 58 (2.7%) of 2130 patients with COVID-19 diagnosed in our hospital;37 (63.8%) were males. Median age was 68.5 years (IQR, 61-75). Main comorbidities were hypertension (28 [48.3%]) and overweight/obesity (23 [39.7%]). Most common SC were prostate (12 [20.7%]), lung (10 [17.2%]) and breast (10 [17.2%]). Overall, 48 (82.8%) patients had previous ECOG PS of 0-1;26 (44.8%) were stage IV and 32 (57.1%) were undergoing cancer treatment. Fifty-six (96.5%) patients were admitted. Most frequent COVID-19 symptoms were fever (40 [69.0%]), cough (35 [62.5%]) and dyspnea (27 [48.2%]). Hydroxychloroquine and azithromycin were used in 40 (69.0%) and 38 (65.5%) patients, respectively;only 3 (5.2%) patients received tocilizumab. Eighteen patients (32.1%) had severe/critical COVID-19. Major complications were respiratory failure (33 [57.9%]), sepsis (14 [24.6%]) and acute kidney injury (13 [22.4%]). Four (6.9%) patients were admitted to ICU. In-hospital and 28-day mortality were 17.2% (10/58) and 24.1% (14/58), respectively. In the multivariate analysis, only dyspnea at diagnosis (hazard ratio [HR]: 6.71, 95% CI 1.40-32.25, p=0.017) and ECOG PS of 2-3 (HR: 4.17;95% CI: 1.13-15.30, p=0.031) were independent risk factors for 28-day mortality. Conclusions: In our patients with SC and COVID-19, 32.1% had a severe/critical disease and 24.1% died within 28 days from diagnosis. Dyspnea at diagnosis and previous ECOG PS of 2-3 were the major predictors for 28-day mortality. Cancer treatment and stage were not associated with mortality. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M. Majem: Honoraria (self), Research grant/Funding (self): BMS;Honoraria (self), Non-remunerated activity/ies: MSD;Honoraria (self), Non-remunerated activity/ies: BOEHRINGER INGELHEIM;Honoraria (self), Non-remunerated activity/ies: ASTRA ZENENCA;Honoraria (self), Non-remunerated activity/ies: KYOWA KYRIN;Honoraria (self): PIERRE FABRE. All other authors have declared no conflicts of interest.