High-risk Febrile Neutropenia Research Articles

Abstract PS11-15: Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain

Abstract Introduction:Prevention of Chemotherapy Induced Neutropenia (CIN) through primary or secondary prophylaxis is indicated in breast cancer (BC) chemotherapy (chemo) which is administered with curative intent. Granulocyte colony stimulating factors (G-CSFs), including Peg are standard of care in this context. In typical every three-week chemo regimens with primary G-CSF prophylaxis, absolute neutrophil count (ANC) nadir occur approximately day (D) 7, which reduces but does not eliminate febrile neutropenia risk in the first week. However, plinabulin (Plin), a novel non-G-CSF agent, protects against the nadir and CIN in the 1st week after chemo (Blayney ASCO 2019). These findings provided the rationale to combine Plin with Peg after chemo with a high febrile neutropenia risk. Both Plin and Peg act on the neutrophil precursor. Both agents mobilize bone marrow-derived CD34+ progenitor stem cells (Blayney ASH 2018). Plin has also anti-cancer efficacy in an animal BC model (Bertelsen, Int J Rad Biol 2011). Here we summarize the efficacy and safety data with combining Peg with Plin in potentially curable BC patients treated with TAC. Methods: In the randomized phase 2 portion of Study 106 (NCT0329457), BC patients were treated with TAC (docetaxel 75, doxorubicin 50 and cyclophosphamide 500 mg/m2) and either 6 mg Peg alone (Peg6; n=22), or Peg 6mg+Plin 20 mg/m2 (Plin+Peg; n=16). Grade (Gr) 3/4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was calculated from absolute neutrophil counts obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire. Percentage of pts with RDI <85% and adverse event rate (Grades 1-5) was calculated. Results: Gr 3 or 4 neutropenia with Plin/Peg vs Peg was 50% vs 81.1% (p<0.04). Median DSMN with Plin/Peg vs Peg was 0.5 day vs 1 day. ANC nadir [mean (95% CI)] with Plin/Peg vs Peg was 1.15 (0.66;1.65) vs 0.80 (0.37;1.22). In the Plin+Peg vs Peg group, Gr 4 AE frequency was 37.3% vs 54.5%, Gr 3 AE frequency was 18.8% vs 27.3%, Gr 2 AE frequency was 25% vs 9.1% and Gr 1 AE frequency was 18.8% vs 4.5%. No Gr 5 AEs occurred in either group. Bone pain was significantly less (P<0.001) with Plin+Peg vs Peg. Conclusion: Addition of Plin to Peg has superior prevention of CIN, superior safety, superior RDI and superior protection against bone pain compared to standard dose Peg alone in this randomized phase 2 trial. A confirmatory global Phase 3 trial comparing Plin+Peg vs Peg alone is underway. RDI<85%Cycle 1Cycle 2Cycle 3Cycle 4Peg0 %13.6 %19.1 %19.1 %Plin+Peg0 %6.25 %6.25 %6.25 % Citation Format: Douglas W. Blayney, Greg Ginn, Lan Huang, Ramon W. Mohanlal. Plinabulin and pegfilgrastim (Plin+Peg) versus peg monotherapy (Peg) after TAC: A comparison of efficacy, safety, relative dose intensity (RDI) and bone pain [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-15.

A Novel Wearable Device for Continuous Temperature Monitoring & Fever Detection.

Objective: Continuous temperature monitoring in high-risk patients can enable healthcare providers to remotely track patients’ temperatures, promptly detect fevers and timely intervene to improve clinical outcomes. We evaluated if a novel wearable, continuous temperature monitor (Verily Patch) can reliably estimate body temperature and early detect fevers in an outpatient setting in patients at a high risk of febrile neutropenia (FN) who recently underwent chemotherapy and autologous stem cell transplantation (ASCT). Methods: 86 patients at a high risk for FN were prospectively enrolled at Mayo Clinic, MN. Patients wore the device in their axilla region for 7 days post ASCT and recorded self-measured oral temperatures every 3 hours. Patients were also followed using clinical standard-of-care procedures with daily oral temperature assessment. The clinic- and patient-assessed oral temperatures were used to develop and evaluate Verily Patch’s body temperature and early fever detection algorithms using a K-fold cross-validation approach. Results: The Verily Patch reliably measured body temperatures with an error of 0.35 ± 0.88°F in comparison to clinic- and patient-assessed oral temperatures. The sensitivity and specificity of the patch in detecting clinic-assessed fever episodes was 90.2% and 87.8%. The patch detected 14.3 times the number of clinic-assessed fever episodes with a median lead time of 4.3 hours. Conclusion: Patient self-monitoring of temperature and fever incidents suffers from low accuracy and is impractical for extended periods of time. Continuous temperature monitoring by a wearable device (such as Verily Patch) has the potential to overcome these challenges resulting in better patient clinical outcomes and more cost-effective care.

Incidence and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using Korean Nationwide Health Insurance Database

PurposeThe aim of this study was to evaluate the episodes of febrile neutropenia (FN) in patients with gastric cancer (GC), colorectal cancer (CRC), lung cancer (LC), and breast cancer (BC); and to identify the incidence and trends of admission rates, as well as factors affecting mortality.Materials and MethodsUsing nationwide claims data, all new admissions to hospitals for FN were selected. We evaluated the incidence of FN and mortality-related clinical factors in adult cancer patients who received cytotoxic chemotherapy from January 2004 to December 2013.ResultsWhile the incidence of FN increased, the length of hospitalization decreased in Korea. The incidence of FN was 19.8% in LC patients, 15.5% in GC patients, 13.3% in BC patients, and 9.5% in CRC patients. The overall in-hospital mortality of FN was 12.9% and showed a decreasing trend. Admission rates to intensive care units and in-hospital mortality were the highest for lung cancer (15.2% and 19.3%, respectively). Age and sepsis syndrome were risk factors for in-hospital mortality for all cancer types.ConclusionCareful observation and active prophylaxis should be considered for patients at high risk of FN.

Antimicrobial de-escalation in patients with high-risk febrile neutropenia: Attitudes and practices of adult hospital care providers.

In a survey of adult hospital providers regarding antibiotic use in the treatment of febrile neutropenia, clinical fellows, and pharmacists showed higher comfort levels with early antimicrobial de-escalation compared to hematology-oncology and transplant infectious diseases physicians. These frontline team members are ideal partners to champion antimicrobial stewardship interventions in febrile neutropenia.

Examining Health-Related Quality of Life in Pediatric Cancer Patients with Febrile Neutropenia: Factors Predicting for Poor Recovery in Children and the Parents

Background: The impact of febrile neutropenia (FN) on the health-related quality of life (HRQoL) of children with cancer is poorly understood. We sought to characterise the course of child and parent HRQoL during and following FN episodes. Method: Data on HRQoL were collected in the multisite Australian PICNICC study. Multiple, discrete FN episodes per patient were allowed. HRQoL was assessed using the Child Health Utility (CHU9D) in children (n=167) and the Assessment of Quality of Life (AQoL-8D) in their parents (N=218) at three time points: 0-3 days, 7-days and 30-days following FN onset. Group-based trajectory modelling (GBTM) was used to characterise the course of HRQoL. Findings: For children, three distinct groups were identified: persistently low HRQoL over 30-days (chronic, 47%), increasing HRQoL from FN onset to 30-days (recovery, 22%), and persistently high HRQoL at all three timepoints (resilient, 32%). Applying these definitions, parents were classified into two distinct groups: chronic (49%) and resilient (51%).The child being male, having solid cancers, the presence of financial stress and relationship difficulties between the parent and child were significant predictors of chronic group membership for parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of being in the resilient group for both parents and children Interpretation: Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child’s sex, cancer type, and presence of financial and relationship stress were predictive of chronic group membership for both parents and children. These families may benefit from increased financial and psychosocial support during anti-cancer treatment. Trial Registration: The Australian PICNICC study is a prospective, multicentre, observational study (Australian New Zealand Clinical Trials Registry 12616001440415). Funding: This study was funded by a National Health and Medical Research Council (NHMRC) Project Grant (APP1104527). Declaration of Interest: GMH was supported by a Victorian Cancer Agency early career fellowship. FEB was part funded by a grant from the Royal Children's Hospital Foundation, Melbourne and the NHMRC. RP was funded by a Post-Doctoral Research Fellow grant from the NIHR, UK (PDF10872). MS has received grants from Merck, Gilead Sciences, F2G and Pfizer. KAT, RDAL, ZA and FM. and RP have no disclosures. Ethical Approval: This study utilised data from the PICNICC RCT, HREC Number (36040A, Royal Children’s Hospital Melbourne Human Research Ethics Committee) and ratified by the UTS HREC (ETH17-1128).

1107. Third Generation Cephalosporins Monotherapy Experience in Pediatric Patients with High-Risk Febrile Neutropenia

BackgroundFever during neutropenia is common in children with cancer. The updated guidelines recommend empirical antibiotic monotherapy using an antipseudomonal ß-lactam, a fourth generation cephalosporin or a carbapenem for high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. In our hospital there are not Pseudomonas aeruginosa isolates in oncology pediatric patients, therefore, we use ceftriaxone as monotherapy in high risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third generation cephalosporins in these patients.MethodsDescriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until December 2019.ResultsWe found 140 episodes in 53 patients, 42 (79%) were leukemia and 11 (21%) solid tumor patients. Of the 140 episodes, 97 (69%) had clinical signs at admission, mostly respiratory in 48 (49%) of the cases. Ninety one (65%) cases started ceftriaxone at admission, 27 (30%) maintained ceftriaxone for 7 days of treatment. Sixty four (70%) cases changed treatment: 38/64 (42%) started second line antibiotics for clinical worsening, 19/64 (20%) required second and third line antibiotics for persistent fever and clinical worsening, and 7/64 (8%) received third line antibiotics from the start for past microbiological history. Eighteen (13%) cases evolved with sepsis requiring intensive care unit management.We had 32 (23%) episodes with positive blood culture, 13 (41%) due to gram positive bacteria, 16 (50%) gram negative bacteria, and 3 (9%) cases of fungal infections. Of the gram negative bacteria, 7 (44%) were ESBL producers, without Pseudomonas aeruginosa isolates.One case died (0.7%) for refractory sepsis due to gram negative bacteria.ConclusionMonotherapy with ceftriaxone is not a good option as initial therapy for high risk febrile neutropenia patients due to the spread of ESBL strains. The empiric therapy has to be evaluated regularly and should always be based in local epidemiology.Disclosures All Authors: No reported disclosures

199. Short versus Extended Antibiotic Treatment with a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients with Fever of Unknown Origin: A Randomized Multicenter Noninferiority Trial

BackgroundIn hematology patients with high risk neutropenia due to intensive chemotherapy the optimal antibiotic treatment duration for fever of unknown origin (FUO) is unknown. Early antibiotic discontinuation has been advocated to reduce unnecessary exposure to broad-spectrum antibiotics, but there is limited evidence for the safety of this strategy. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment for neutropenic patients with FUO.MethodsMulticenter, open-label, randomized clinical trial in 6 centers in the Netherlands. Hematology patients with FUO during high risk neutropenia (≥7 days) were eligible for participation. Eligible patients who gave informed consent were randomly assigned (1:1) to either the short treatment arm, where the carbapenem was discontinued after 72 hours, irrespective of presence of fever, or the extended treatment arm, where the carbapenem was continued for ≥ 9 days until afebrile for 5 days or end of neutropenia (EON), whichever came first. The primary endpoint was treatment failure defined as a composite of recurrent fever or a carbapenem-sensitive infection between day 4 and day 8 and septic shock or death from day 4 until EON. Secondary endpoints included all-cause and infection-related mortality until 30 days post-EON. We used 10% as noninferiority margin.Trial Intervention Flowchart ResultsBetween December 2014 and August 2019 292 patients were included. Risk of treatment failure in the modified intention-to-treat analysis (mITT) was 23.5% (32/136) in the short treatment versus 18.3% (24/131) in the extended treatment arm (adjusted risk difference (ARD) 3.7% (90% CI -2.6% to 9.9%)) and in the per-protocol analysis 27.9% (29/104) versus 18.2% (22/121) (ARD 8.9% (90% CI 0.6% to 17.2%). Short treatment was non-inferior to extended treatment in the mITT population, but not in the per protocol population.All-cause mortality until 30 days post-EON was significantly higher in the short treatment group: 3.7% (5/136) versus 0.8% (1/131) (ARD 2.8%, 95% CI 1.3 to 4.4%), but infection-related mortality until 30 days post-EON was not statistically different between the treatment arms.Primary and Secondary Endpoint Results Subgroup Analyses Results Bloodstream infections after day 3 ConclusionShort treatment with a carbapenem in neutropenic patients with fever was noninferior to extended treatment with regard to treatment failure.Conclusion Summary Disclosures All Authors: No reported disclosures

The prevalence of neutropenia in chemotherapy cancer patients at a provincial hospital, Thailand

Abstract Introduction Cancer patients with neutropenia (<1500 cell/mm3 absolute neutrophil count [ANC]) are at high risk of febrile neutropenia and serious complications which can cause the delay treatment, reduction of chemotherapy dose, leading to morbidity and mortality. We lack of information of the prevalence of neutropenia in Thailand and its' consequences. Thus, this cross-sectional study aimed to investigate the prevalence of neutropenia at a provincial hospital in northern Thailand. Methods We retrospectively reviewed electronic medical records of cancer patients with solid tumor and receiving chemotherapy from September 2018 to October 2019. Results A total of 248 cancer patients (79 men, 169 women, mean age of 58.36±12.03) were included. The top 3 cancers were colon, breast and lung cancer (50.53%, 34.33%, 6.88%). They received chemotherapy 1,803 cycles of treatment. The top 3 regimens of treatment were FOLFOX (oxaliplatin/ fluorouracil/ leucovorin), AC (doxorubicin/ cyclophosphamide) and paclitaxel (42.65%, 17.75%, 9.67%). The prevalence of neutropenia (<1500 cell/mm3) was 264 episodes: 64 episodes of ANC 1,000-1,500 cell/mm3 (3.55%); 172 episodes of ANC 500-1,000 cell/mm3 (9.54%); and 28 episodes of ANC <500 cell/mm3 (1.55%). Most of them were postponed the treatment, but 16 episodes were still received chemotherapy. The dose of chemotherapy in 78 episodes were decreased and 16 episodes were related to the treatment of febrile neutropenia. The treatment of febrile neutropenia chemotherapy patients was 8 + 3 days with an average of US$ 400 per person, per cost of treatment. Conclusions We found that the effects of neutropenia in chemotherapy patients were delayed treatment, dose reduction and a major risk factor of febrile neutropenia. This decreased the efficiency of chemotherapy in patients with cancer. The result should be informed and encouraged our patient care team to develop practical action for prevention and management of serious neutropenic events. Key messages The result should be informed and encouraged our patient care team to develop practical action for prevention and management of serious neutropenic events. If we can manage cancer patients with neutropenia, the cost of treatment for serious febrile neutropenia and other complications will be reduced.

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

1715P Plinabulin (Plin) is a more favorable option for the prevention of chemotherapy induced neutropenia (CIN) than pegfilgrastim (Peg) during the COVID-19 pandemic

Due to COVID-19, the NCCN Myeloid Growth Factor Panel expanded prophylactic G-CSF use to chemotherapy with Intermediate Risk (10%-20% risk) of Febrile Neutropenia (FN), and to Low Risk FN patients (pts) who previously developed FN. Preservation of resources for COVID-19 pts by reducing hospitalizations and emergency room visits by cancer chemotherapy pts is the intent of these changed recommendations. Other recommendations include use of self-injecting or on-body injector Peg, to minimize COVID-19 exposure at outpatient center by cancer pts and limiting prophylactic platelet transfusion to preserve blood product supply. Plin is an attractive alternative: it is a novel, non-G-CSF small molecule with CIN protection comparable to Peg, is given once 30 minutes after Chemo, and avoids the need for healthcare system touches on Day 1-3 for G-CSF administration. In contrast to Peg, Plin does not cause bone pain and thrombocytopenia and maintains quality of life. We compared the combined CIN data with single agent (SA) Plin 20 mg/m2 (n=29) vs. SA Peg 6mg (n=35) from 2 different phase II CIN studies over 4 cycles: 1. Study 105 in NSCLC pts given Intermediate FN Risk Docetaxel 75 mg/m2 (Doc) pts with risk factors), and 2. Study 106 in Breast cancer pts given High FN Risk Doc +Doxorubicin 50 mg/m2 + Cyclophosphamide 50mg/m2 (TAC). Plin was given as a single IV infusion on Day (D)1, 30 min after the last Chemo, and Peg 6mg given on D2 by SC injection. Grade 4 Neutropenia (Gr 4 N), Hospitalizations (Hosp), Infection rate (Inf), Sepsis (Sep), all Grade Thrombocytopenia (T) or Gr 2/3 T and Bone Pain (BoP) is summarized for SA Plin and SA Peg. (NS= non-significant). Table: 1715PGr 4 NHospInfSepAll Gr TGr 2/3 TGr 3 TBoPPegfilgrastim42.9%11.4%5.71%0%68.6%20%8.57%YesPlinabulin44.8%13.8%6.90%3.44%24.1%3.4%0%Nop-valueNSNSNSNS0.00020.0250.06- Open table in a new tab . Plin requires at least 50% fewer touches to the health care system and is equally effective as Peg for prevention of CIN and its clinical sequelae. Plin causes less thrombopenia and bone pain. Plin (given as a 40 mg fixed dose) is currently in two phase III trials for CIN.

Clinical characteristics and microbiological profile of viridans group streptococci bacteremia in children with cancer and high-risk febrile neutropenia

Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity. To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile. Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains. 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to β lactams. As expected, there were not non-susceptible strains to vancomycin. VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to β lactams is an issue that requires strict epidemiological surveillance in this population.

Insertion site of central venous catheter correlates with catheter-related infectious events in patients undergoing intensive chemotherapy.

Patients undergoing intensive chemotherapy are usually in need for central venous catheters (CVC). Due to contradictory study results, relation of insertion site and CVC-associated complication rate in these patients is not clear. We therefore retrospectively analyzed CVC-related data of all patients undergoing intensive chemotherapy with high risk of febrile neutropenia according to NCCN criteria, who received a CVC at our bone marrow transplantation unit between May 2016 and December 2019. In total, 210 patients received 281 CVC. CVC were placed via either the subclavian-vein (SCV, n = 58; 20%) or the internal-jugular-vein (IJV, n = 223; 80%). Median duration of CVC-lifetime and neutropenic days per CVC were comparable between the two groups (IJV vs SCV: 23 days vs 21 days (p = 0.16) and 12 days vs 11 days (p = 0.65)). Both, time to CVC removal due to local inflammation and time to central line-associated bloodstream infection was significantly shorter in patients with SCV catheters (p = 0.013 and p = 0.045). CVC placed in the IJV were associated with significantly less catheter-related infectious events compared with CVC placed in the SCV. This difference was consistent across different subgroups including 88 patients undergoing allogeneic stem cell transplantation.

Usefulness of serum galactomannan in initiating and modifying antifungal therapy in children with cancer and persistent high-risk febrile neutropenia.

Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population. To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds. A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P=.99). A difference threshold in sGM Δ≥0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P=.04). Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

Validation of Risk of Chemotherapy-Induced Neutropenia: Experience from Oncology Hospital of Nepal.

BackgroundThe majority of cancer patients undergoing chemotherapy show neutropenic condition which is a common side effect of myelosuppressive chemotherapy diagnosed as the reduced complete blood cell count. Such cancer patients have a higher risk of febrile neutropenia. The present study aimed to validate whether there was a risk of neutropenia in cancer patients receiving chemotherapy at Bhaktapur Cancer Hospital, Nepal.MethodsCross-sectional study was performed among 203 cancer patients of all age groups who attended Bhaktapur Cancer Hospital from May 2018 to January 2019 and who received a chemotherapy course. Patients receiving at least one cycle of chemotherapy as the first-line treatment were included. Statistical analysis was performed using SPSS 25. Loglinear analysis was used to analyze more than 2×2 categories among the grades and outcome of neutropenia. Multinomial logistic regression was applied to analyze the impact of various predictor variables such as chemotherapy cycles, grades of neutropenia, and gender on the outcome of neutropenia. Variation in the absolute neutrophil count (ANC) level at various days of chemotherapy cycles was assessed with the multivariate analysis of variance (MANOVA). The p-value <0.05 was considered significant at each condition.ResultsThe main cancer type during the study period was breast cancer (41, 20.2%). Out of 163 neutropenic patients, 149 had severe neutropenia and 14 had mild neutropenia. Most patients were continued up to the 6th cycle of chemotherapy. There was significant association between the grade of neutropenia and the outcome of the condition (p-value 0.017). There were significant relations of the grade of neutropenia and smoking habit with the recovering status (p values 0.033 and 0.001, respectively). The absolute neutrophil count (ANC) level increased and decreased inconsistently (statistically non-significantly) in between treatment period of day 1 to 52.ConclusionChemotherapy-induced neutropenia was a common occurrence. Majority (133, 66.5%) grade 4 neutropenic patients were recovering after the chemotherapy cycles. The physicians are warranted that they be ready for any unpredictable situation during chemotherapy treatment.

Trends in use of primary prophylactic colony stimulating factors and neutropenia-related hospitalization in commercially insured patients receiving myelosuppressive chemotherapy in the United States: 2005-2017.

Describe temporal changes in use of myelosuppressive chemotherapy, primary prophylactic colony-stimulating factor, and neutropenia-related hospitalization, in commercially insured patients. Using a large commercial administrative database, we identified annual cohorts of adult patients diagnosed with breast or lung cancer, or non-Hodgkin lymphoma and initiating myelosuppressive chemotherapy during 2005-2017. We described yearly changes in proportions of myelosuppressive chemotherapy by febrile neutropenia risk category (high, intermediate, unclassified) and proportion of prophylactic colony-stimulating factor use and unadjusted incidence of neutropenia-related hospitalization in the first cycle of myelosuppressive chemotherapy. Annual cohorts included 4383-5888 eligible patients during 2005-2017. The proportion of eligible patients aged ≥ 65 years increased from 26.0% in 2005 to 58.2% in 2017. Myelosuppressive chemotherapy use with regimens with high risk for febrile neutropenia increased from 15.1% in 2005 to 31.0% in 2017; and regimens with intermediate risk for febrile neutropenia decreased from 63.7% to 48.1% in 2017. Prophylactic colony-stimulating factor use increased from 41.6% in 2005 to 54.3% in 2017. Crude incidence of neutropenia-related hospitalization for all cancers increased from 2.0% to 3.1%, with a substantial increase in neutropenia-related hospitalization observed among non-Hodgkin lymphoma patients (2.8% to 8.5%) during 2005-2017. Among adult patients with breast and lung cancer, and non-Hodgkin lymphoma receiving myelosuppressive chemotherapy, use of regimens with high risk for febrile neutropenia increased, as did the use of prophylactic colony-stimulating factors after 2005. Incidence of neutropenia-related hospitalization increased slightly, particularly among non-Hodgkin lymphoma patients. Further studies are required to understand this increasing trend of neutropenia-related hospitalization, changing patient-level risk factors, and febrile neutropenia management.

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer.

FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC. We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea. Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors. Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

Abstract P5-14-12: Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector

Abstract Introduction: Use of pegfilgrastim in patients who are at high risk of febrile neutropenia (&amp;gt;18%) results in a 94% reduction in febrile neutropenia. Use of pegfilgrastim is also associated with increased chemotherapy Relative Dose Intensity (RDI) due to fewer dose reductions, delays and discontinuations. Higher RDI has been associated with increased survival. Pegfilgrastim use historically required patients to return the day after chemotherapy. Introduction of the on-body injector (OBI) allows for next day delivery of growth factor without patients having to come back to the clinic. We conducted a study comparing neutropenia rates, dose delays and total cost of care for breast cancer patients receiving chemotherapy with high risk of febrile neutropenia who received (1) no pegfilgrastim, (2) pegfilgrastim via pre-filled syringe (PFS), (3) pegfilgrastim via OBI. Methods: The data utilized for this study originates from the EHRs, practice management systems and CMS claims obtained as part of the Oncology Care Model (OCM) for eight practices supported by Integra Connect Population Health. Using our harmonized data model, DTX, we constructed synthetic chemotherapy episodes of care. Each episode began with an administration of a chemotherapy regimen defined as having a high risk of febrile neutropenia per NCCN. The episode ended the day of the next chemotherapy administration, or after 14 days if no subsequent chemotherapy was given. Each episode was assigned to a cohort, no pegfilgrastim, pegfilgrastim via PFS, or pegfilgrastim via OBI. To evaluate the efficacy and toxicity associated with pegfilgrastim administration, we conducted a matched cohort analysis. Patients were matched based on age, sex, cancer type, number of comorbidities, regimen, chemo start date (within 90 days), whether the administration was the last cycle of chemotherapy, and OCM provider quality metrics. Results: Compared with no pegfilgrastim, PFS episodes had 9.9% less grade IV neutropenia (ANC &amp;lt; 500, p &amp;lt; 0.001) and 5.6% fewer dose delays (p=0.0014, n=916 in each arm). Compared with OBI, PFS episodes had 0.3% less grade IV neutropenia (p=0.47) and 5.3% fewer dose delays (p=0.009, n=2,727 in each arm). Exploratory analysis highlighted differences in physician office and hospital utilization. PFS episodes include more non-chemotherapy office visits than OBI episodes (2.1 vs 1.3, p &amp;lt; 0.001). PFS patients are more likely to have an unplanned office visit (64% vs 23%, p &amp;lt; 0.001) and more likely to receive hydration during an episode (34% vs. 21%, p = 0.021). PFS episodes include less hospital utilization compared with OBI episodes. OBI episodes are 23% more likely to include hospitalization (5.0% vs 6.2%, p=0.031). Discussion: As expected, this observational real-world analysis shows that the use of pegfilgrastim via PFS or OBI is associated with reduced neutropenia rates and reduced dose delays compared with no pegfilgrastim. Comparing PFS with OBI, we see similar neutropenia rates, but PFS shows fewer dose delays and fewer hospitalizations. Exploratory analysis provides some insight into these dose delays and related health care utilization. Our analysis shows that patients returning next day to the cancer center to receive pegfilgrastim frequently receive other services such as labs and hydration. These services lead to fewer dose delays, perhaps because toxicities other than neutropenia are detected earlier in the episode and can be managed in the office. This implies that use of PFS may be used as part of a strategy to shift site of service for management of side effects into the physician office and away from hospitals and emergency departments. Citation Format: Jennifer Webster, Jeffrey Scott, Danielle Wieland, Joseph Donaldson, Ash Malik, Rushir Choksi. Patients receiving pegfilgrastim via prefilled syringe received closer care when compared with on-body injector [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-12.

Abstract P2-08-24: Risk of chemotherapy-induced febrile neutropenia (FN) in patients with metastatic cancer of the breast or other sites not receiving colony-stimulating factor prophylaxis (CSF) in US clinical practice

Abstract Background: Clinical practice guidelines recommend CSF prophylaxis for patients receiving chemotherapy regimens with a high risk of FN (&amp;gt;20%), and consideration of CSF prophylaxis for those receiving intermediate-risk regimens (10-20%) who have ≥1 risk factor for FN. The objective of this study was to estimate the use of CSF prophylaxis among patients with metastatic cancer, and the risk of FN among eligible patients not receiving it. Methods: This retrospective study was conducted at four US health systems—Geisinger Health System (PA), Henry Ford Health System (MI), Kaiser Permanente Northwest (OR, WA), and Reliant Medical Group (MA). Study population comprised patients who received chemotherapy for metastatic solid tumors (breast, colon/rectum, lung) or non-Hodgkin’s lymphoma (NHL) from 2009-2017. For each eligible patient, data on chemotherapy course, cycles, and regimens, as well as the use of supportive care (CSF, antimicrobials) and FN episodes during the course, were collected via a standardized case report form using electronic data warehouses, cancer registries, and medical charts. Analyses were non-comparative and descriptive only. Results: Study population totaled 1,457 patients (26% breast; 25% colon/rectum; 43% lung; 6% NHL). Nearly half of all patients received a chemotherapy regimen classified as either high-risk for FN (21%), or intermediate-risk for FN and had ≥1 FN risk factor (28%). Among patients receiving high-risk regimens, 51% did not receive primary prophylaxis with CSF (PP-CSF), and among those receiving an intermediate-risk regimen with ≥1 risk factor, 86% did not receive PP-CSF; among all remaining patients, 89% did not receive PP-CSF. Across these three subgroups of patients who did not receive PP-CSF (ie, high-risk regimen, intermediate-risk regimen with ≥1 risk factor, all others), FN risk during the course was 17%, 16%, and 14%, respectively. More than 90% of FN episodes required hospitalization, and FN-related mortality was 14%. Among metastatic breast cancer patients, 56% received a high-risk regimen (46%) or an intermediate-risk regimen and had ≥1 FN risk factor (10%); among this subset, 30% did not receive PP-CSF and their FN risk was 16%. Conclusions: In this real-world evaluation of patients with metastatic cancer of the breast or other sites receiving chemotherapy at four large US health systems, over two-thirds of patients who were candidates for PP-CSF (per clinical guidelines) did not receive it. Among the subset of candidates who did not receive PP-CSF, FN risk was high (16%) and associated consequences were severe. Careful consideration should be given to identifying metastatic patients at elevated risk of FN—based on their chemotherapy regimen and risk factors—to ensure appropriate use of supportive care. Table. FN risk factors and chemotherapy FN risk level among metastatic patientsBreast Cancer (N = 380)Colorectal Cancer (N = 360)Lung Cancer (N = 626)NHL (N = 91)All (N = 1,457)FN Risk FactorsAge ≥65y, %20.821.137.240.729.2Prior chemotherapy or radiation therapy, %39.234.248.445.142.3Prior neutropenia, %1.82.22.69.92.7Bone marrow involvement, %27.12.830.024.222.2Recent surgery, %40.042.216.914.329.0Liver dysfunction (bilirubin &amp;gt;2.0), %0.81.40.50.00.8Renal dysfunction (creatinine clearance &amp;lt;50), %45.362.259.365.956.8Chemotherapy FN Risk Level, %High45.80.017.417.620.5Intermediate10.554.726.450.530.7Low8.922.541.20.025.6Unclassified34.722.815.031.923.1 Citation Format: Derek Weycker, Amanda Silvia, Ahuva Hanau, Lois Lamerato, Kathryn Richert-Boe, Manpreet Kaur, Neel Shah, Mark Hatfield, Gary H Lyman. Risk of chemotherapy-induced febrile neutropenia (FN) in patients with metastatic cancer of the breast or other sites not receiving colony-stimulating factor prophylaxis (CSF) in US clinical practice [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-24.

Patterns of granulocyte colony\u2013stimulating factor prophylaxis in patients with cancer receiving myelosuppressive chemotherapy

PurposeTo evaluate patterns of primary prophylactic (PP) granulocyte colony–stimulating factor (G-CSF) use following chemotherapy by cancer type and febrile neutropenia (FN) risk.MethodsUsing a commercial administrative database, we identified adult patients diagnosed with breast, colorectal, lung, ovarian cancer, or non-Hodgkin lymphoma (NHL) who initiated chemotherapy with high risk (HR) or intermediate risk (IR) for FN between January 1, 2013, and August 31, 2017. We describe use of PP-G-CSF, proportion completing all their cycles with pegfilgrastim, timing of pegfilgrastim, and duration of short-acting G-CSF.ResultsAmong 22,868 patients (breast 11,513; colorectal 3765; lung 4273; ovarian 1287; and NHL 2030), 36.8% received HR and 63.2% received IR (64.4% of whom had ≥ 1 risk factor [RF] for FN). Proportions of patients receiving PP-G-CSF in the first cycle were 76.1%, 28.2%, and 26.4% among patients receiving HR, IR, and IR plus ≥ 1 RF, respectively. Among breast cancer patients receiving HR regimens and initiating PP-pegfilgrastim, 60.4% (95% confidence interval [CI] 57.2–63.6%) initiating via on-body injector (OBI) and 51.9% (95% CI 48.0–55.8%) initiating via prefilled syringe (PFS) completed all their cycles with OBI and PFS, respectively. Among all cycles with PP-PFS, 8.5% received PFS on the same day as chemotherapy completion. Mean administrations/cycle were 3.2 (standard deviation [SD] 2.3) for filgrastim, 3.0 (SD 1.6) for filgrastim-sndz, and 4.3 (SD 2.5) for tbo-filgrastim.ConclusionsThere is under- and mistimed use of PP-G-CSF among patients at HR for FN. Novel pegfilgrastim delivery devices could help breast cancer patients at HR for FN complete all their cycles with timely prophylaxis.