The impact of new and emerging agents on outcomes for febrile neutropenia: addressing clinical gaps.

PURPOSE OF REVIEW: While chemotherapy treatment options for patients with solid and hematologic malignancies have dramatically improved over recent years, chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) remain major barriers to delivering treatment at full doses and optimal timing. Despite concurrent advances in granulocyte colony-stimulating factor (G-CSF) administration, multiple barriers to the administration of and disparities in the access to these agents remain. The introduction of new, emerging agents, including biosimilars and novel therapies show promise in improving outcomes for CIN. RECENT FINDINGS: The introduction of biosimilar filgrastim products has improved access to G-CSF administration by driving marketplace competition and has reduced costs for both patients and healthcare systems without sacrificing efficacy. Emerging therapies to address similar issues include long-acting G-CSF products, efbemalenograstim alfa and eflapegrastin-xnst, as well as agents with novel mechanisms of action, plinabulin and trilaciclib. These agents have shown efficacy and cost-saving benefits in certain populations and disease groups. SUMMARY: Multiple emerging agents show promise in decreasing the burden of CIN. Use of these therapies will reduce access disparities and will improve outcomes for patients with cancer receiving cytotoxic chemotherapy. Many ongoing trials are underway to evaluate the roles of these agents for more widespread use.

Associations between body mass index, weight loss and overall survival in patients with advanced lung cancer.

BACKGROUND: Weight loss (WL) has been associated with shorter survival in patients with advanced cancer, while obesity has been associated with longer survival. Integrating body mass index (BMI) and WL provides a powerful prognostic tool but has not been well-studied in lung cancer patients, particularly in the setting of clinical trials. METHODS: We analysed patient data (n = 10 128) from 63 National Cancer Institute sponsored advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) trials. Risk matrices were created using BMI and WL percentage, which were divided into 'grades' based on median survival. Relationships between survival, BMI and WL percentage were examined using Kaplan-Meier estimators and Cox proportional hazards (PH) models with restricted cubic splines. RESULTS: For NSCLC, a twofold difference was noted in median survival between the BMI > 28 and WL ≤ 5% group (13.5 months) compared with the BMI < 20 and WL > 5% group (6.6 months). These associations were less pronounced in SCLC. Kaplan-Meier curves showed significant survival differences between grades for both NSCLC and SCLC (log-rank, P < 0.0001). In Stage IV NSCLC, Cox PH analyses with restricted cubic splines demonstrated significant associations between BMI and survival in both WL ≤ 5% (P = 0.0004) and >5% (P = 0.0129) groups, as well as in WL > 5% in Stage III (P = 0.0306). In SCLC, these relationships were more complex. CONCLUSIONS: BMI and WL have strong associations with overall survival in patients with advanced lung cancer, with a greater impact seen in NSCLC compared with SCLC. The integration of a BMI/WL grading scale may provide additional prognostic information and should be included in the evaluation of therapeutic interventions in future clinical trials in advanced lung cancer.

Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events.

The mechanisms underlying tumor immunosurveillance and their association with the immune-related adverse events (irAEs) associated with checkpoint inhibitor immunotherapies remain poorly understood. We describe a metastatic melanoma patient exhibiting multiple episodes of spontaneous disease regression followed by the development of several irAEs during the course of anti-programmed cell death protein 1 antibody immunotherapy. Whole-exome next-generation sequencing studies revealed this patient to harbor a pyrin inflammasome variant previously described to be associated with an atypical presentation of familial Mediterranean fever. This work highlights a potential role for inflammasomes in the regulation of tumor immunosurveillance and the pathogenesis of irAEs.

Heart rate is an independent predictor of all-cause mortality in individuals with type 2 diabetes: The diabetes heart study.

AIM: To assess the association of resting heart rate with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study (DHS). METHODS: Out of a total of 1443 participants recruited into the DHS, 1315 participants with type 2 diabetes who were free of atrial fibrillation and supraventricular tachycardia during the baseline exam were included in this analysis. Heart rate was collected from baseline resting electrocardiogram and mortality (all-cause and CVD) was obtained from state and national death registry. Kaplan-Meier (K-M) and Cox proportional hazard analyses were used to assess the association. RESULTS: The mean age, body mass index (BMI) and systolic blood pressure (SBP) of the cohort were 61.4 ± 9.2 years, 32.0 ± 6.6 kg/m2, and 139.4 ± 19.4 mmHg respectively. Fifty-six percent were females, 85% were whites, 15% were blacks, 18% were smokers. The mean ± SD heart rate was 69.8 (11.9) beats per minute (bpm). After a median follow-up time of 8.5 years (maximum follow-up time is 14.0 years), 258 participants were deceased. In K-M analysis, participants with heart rate above the median had a significantly higher event rate compared with those below the median (log-rank P = 0.0223). A one standard deviation increase in heart rate was associated with all-cause mortality in unadjusted (hazard ratio 1.16, 95%CI: 1.03-1.31) and adjusted (hazard ratio 1.20, 95%CI: 1.05-1.37) models. Similar results were obtained with CVD mortality as the outcome of interest. CONCLUSION: Heart rate is an independent predictor of all-cause mortality in this population with type 2 diabetes. In this study, a 1-SD increase in heart rate was associated with a 20% increase in risk suggesting that additional prognostic information may be gleaned from this ubiquitously collected vital sign.