Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4,447 cancer patients treated with ICI antibodies, 37 (0.8%) [23 men (62.2%), mean age 64.7 ± 8.3 years (range 46-79 yr)] were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n=20, 54.1%), followed by melanoma (n=8, 21.6%). The most commonly ICI antibody inhibitor reported was nivolumab (n=18, 48.6%), pembrolizumab (n=16, 43.2%) and ipilimumab (n=8, 21.6%). About half of the patients (n=19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n=10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5-12) after starting immunotherapy. The main reported symptom at presentation was fatigue (97.3%), followed by anorexia (81.8%) and general malaise (81.1%). Mean follow-up time since IAD diagnosis was 15.2 ± 12.5 months (range 0.3-55 months). At last visit all patients continued with hormonal deficiency of ACTH. Median overall survival since IAD diagnosis was 6.0 months. In conclusion, IAD is a rare but a well-established complication associated with ICI therapy in cancer patients. It develops around 7 months after starting treatment, mainly anti-PD1 antibodies. Recovery of the corticotropic axis function should not be expected.

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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, p¼0.017) and ECOG PS of 2-3 (HR: 4.17; 95% CI: 1.13-15.30, p¼0.031) 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.

2551 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 (proinflam-status), 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: see text]

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