Infectious Complications in Patients With Non-small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are standard treatment for nonsmall cell lung cancer (NSCLC). However, the burden of infectious complications during ICI therapy is poorly described. MATERIALS AND METHODS: We conducted a retrospective study of patients with NSCLC treated with ICIs between 2007 and 2020 at a tertiary academic center. The incidence, characteristics, and healthcare utilization outcomes of infections during ICI therapy and within 3 months of ICI discontinuation are presented using descriptive statistics. Cox proportional hazard models are used to examine infection-free survival by demographic and treatment factors. Associations between patient or treatment characteristics and hospitalization or ICU admission are analyzed by logistic regression, presented as odds ratios (OR). RESULTS: Of 298 patients, infections occurred in 54.4% (n = 162). Of these patients, 59.3% (n = 96) required hospitalization and 15.4% (n = 25) required ICU admission. The most common infection was bacterial pneumonia. Fungal infections occurred in 12 patients (7.4%). Patients with chronic obstructive pulmonary disease (COPD) (OR 2.15, 95% CI, 1.01-4.58), corticosteroid treatment within 1 month prior to infection onset (OR 3.04, 95% CI, 1.47-6.30), and concomitant irAE and infection (OR 5.48, 95% CI, 2.15-14.00) had higher odds of hospitalization. Corticosteroid use was associated with higher odds of ICU admission (OR 3.09, 95% CI, 1.29-7.38). CONCLUSION: In this large single-institution study we identify that more than half of patients with ICI-treated NSCLC develop infectious complications. We identify that patients with COPD, recent corticosteroid use, and concomitant irAE and infection have higher odds of hospitalization, and that unusual infections (eg, fungal) can occur. This highlights clinical awareness of infections as important complications during ICI therapy in patients with NSCLC.

Interleukin-18 and tumor necrosis factor-α are elevated in solid organ transplant recipients with possible cytomegalovirus end-organ disease.

End-organ cytomegalovirus (CMV) disease can be life threatening to solid organ transplant recipients. Diagnosis is often complicated by variation in amount of CMV DNA in plasma and the need for an invasive procedure to obtain a biopsy of the suspected affected organ, which can delay recognition and treatment. Several inflammatory cytokines are elevated in CMV disease, and the purpose of this study was to determine if they could be used to distinguish solid organ transplant recipients with CMV DNAemia alone from those with possible end-organ CMV disease. We found that regardless of pre-transplant CMV serostatus, plasma interleukin (IL)-18, tumor necrosis factor-α (TNF-α), and amount of CMV DNA in plasma were increased in possible end-organ CMV disease, with elevated IL-18 associated with increased odds of possible end-organ CMV disease even after adjusting for amount of CMV DNA. These findings highlight IL-18 and TNF-α as potential non-invasive markers of possible end-organ CMV disease regardless of transplanted organ or serostatus in solid organ transplant recipients.

A Comprehensive Evaluation of Risk Factors for Pneumocystis jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. METHODS: A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). RESULTS: A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. CONCLUSIONS: PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.