Immunological Characteristics of Hyperprogressive Disease in Patients with Non-small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Abs

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

Immunological Characteristics of Hyperprogressive Disease in Patients with Non-small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Abs

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

A Retrospective Analysis of Characteristics of Probiotics Associated with Invasive Bacterial Infections in Children

PURPOSE: The purpose of this study was to analyze the clinical features and risk factors of invasive infections caused by Lactobacillus spp. and Saccharomyces spp., components of commercially available probiotics. METHODS: We analyzed demographic and clinical data from children ≤18 years of age with an invasive infection caused by Lactobacillus spp. or Saccharomyces spp. at the Asan Medical Center Children's Hospital from January 1998 to June 2016. Probiotic consumption data were also analyzed. RESULTS: During the study period, a total of 24 episodes of invasive infections were caused by Lactobacillus spp. (n=16) and Saccharomyces cerevisiae (n=8). Along with the increase of probiotic use (755,594 [days/1,000 patient-admission days] in 2001 to 2005, 1,444,066 in 2006 to 2010, and 6,904,736 in 2011 to 2016), the incidence of probiotic-associated invasive infection increased (R2=0.70). The median age of the patients was 1.8 years (range, 2 months to 17 years), and most of them had underlying medical conditions. The 30-day mortality rate was 20.8% (5/24), and 11 (45.8%) of these patients resulted from a severe invasive infection. We determined the risk factors for invasive infection to be: previous intensive care unit stay (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.5 to 6.1] and the presence of a central venous catheter (OR, 2.2; 95% CI, 1.2 to 4.3). CONCLUSIONS: Although the probiotic-associated invasive infections rarely occurred in children, the incidence has increased along with probiotic pressure. Judicious use of probiotics is mandatory, especially in young children with underlying medical conditions and continuous surveillance will be needed to minimize the safety concerns.

A Retrospective Analysis of Characteristics of Probiotics Associated with Invasive Bacterial Infections in Children

PURPOSE: The purpose of this study was to analyze the clinical features and risk factors of invasive infections caused by Lactobacillus spp. and Saccharomyces spp., components of commercially available probiotics. METHODS: We analyzed demographic and clinical data from children ≤18 years of age with an invasive infection caused by Lactobacillus spp. or Saccharomyces spp. at the Asan Medical Center Children's Hospital from January 1998 to June 2016. Probiotic consumption data were also analyzed. RESULTS: During the study period, a total of 24 episodes of invasive infections were caused by Lactobacillus spp. (n=16) and Saccharomyces cerevisiae (n=8). Along with the increase of probiotic use (755,594 [days/1,000 patient-admission days] in 2001 to 2005, 1,444,066 in 2006 to 2010, and 6,904,736 in 2011 to 2016), the incidence of probiotic-associated invasive infection increased (R2=0.70). The median age of the patients was 1.8 years (range, 2 months to 17 years), and most of them had underlying medical conditions. The 30-day mortality rate was 20.8% (5/24), and 11 (45.8%) of these patients resulted from a severe invasive infection. We determined the risk factors for invasive infection to be: previous intensive care unit stay (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.5 to 6.1] and the presence of a central venous catheter (OR, 2.2; 95% CI, 1.2 to 4.3). CONCLUSIONS: Although the probiotic-associated invasive infections rarely occurred in children, the incidence has increased along with probiotic pressure. Judicious use of probiotics is mandatory, especially in young children with underlying medical conditions and continuous surveillance will be needed to minimize the safety concerns.