Rates Of Neutropenia Research Articles

A Comparison of Acute Myeloid Leukemia (AML) Regimens: Hypomethylating Agents Combined with Ivosidenib or Venetoclax in Newly Diagnosed Patients with IDH1 Mutations: A Real-World Evidence Study

Background: Two frontline combination regimens are available for patients with mutant IDH1 (mIDH1) AML: ivosidenib (IVO)+hypomethylating agent (HMA), and venetoclax (VEN)+HMA. Robust comparisons between these regimens have not been performed, and small post hoc analyses have been constrained by low numbers of mIDH1 patients and clustering of IDH1 and IDH2 mutations (Pollyea 2022, Perl 2022). We evaluated a large cohort of patients with newly diagnosed (ND) mIDH1 AML to gain insights into the treatment patterns, efficacy, and safety associated with these combination regimens. Methods: We conducted a US-wide retrospective chart review of patients with ND mIDH1 AML ineligible for intensive chemotherapy (IC), treated with IVO+HMA or VEN+HMA. Treatment was initiated in community and academic settings November 2021 through November 2022, enabling a minimum follow-up of 6 months. Collected data included baseline patient and practice characteristics, treatment patterns and rationale, and efficacy and safety outcomes. Endpoints focused on events likely to occur within 6 months of follow-up, including response rates, tolerability, bridge to transplant, and acute care episodes. Results: Among 283 patients (IVO+HMA, n=182; VEN+HMA, n=101), baseline characteristics were similar between regimens. Median age was 63 years; 65.7% were male. ELN cytogenetic risk status was 59.7% and 15.2% for intermediate and poor, respectively. Prior MDS, myeloproliferative neoplasms, or secondary or secondary-like AML mutations occurred in 37.1%. A higher proportion of VEN+HMA use occurred in the academic setting (68.3% vs 55.5% for IVO+HMA; p=0.035). Median follow-up from treatment initiation was 7.1 vs 8.1 months for IVO+HMA vs VEN+HMA. Complete response (CR) plus CR with incomplete count or incomplete platelet recovery (CRi/p) rates were 63.2% vs 49.5% for IVO+HMA vs VEN+HMA ( p=0.025), with the difference based on the higher CR rate for IVO+HMA (42.9% vs 26.7%; p=0.007) (Figure). Median time to first bone marrow biopsy on treatment across cohorts was 56 days and median time to best response was 3.3 vs 4.1 months for IVO+HMA vs VEN+HMA ( p=0.002). A competing risks regression showed that 6-month event-free survival (EFS; CR within 24 weeks, and no relapse or death) favored IVO+HMA vs VEN+HMA (56.0% vs 39.6%, hazard ratio of 0.773; p=0.044). Bridge to transplant was achieved for 11.5% of patients with IVO+HMA vs 5.0% for VEN+HMA ( p=0.066). Few patients in either cohort had a dose (ie, strength) change following initial ramp-up. Treatment discontinuation was 37% for both regimens. Likewise, toxicity incidence was similar except for higher febrile neutropenia (FN) rates for VEN+HMA vs IVO+HMA within 30 days of initiation (7.9% vs 1.6%; p=0.009). Patients receiving IVO+HMA had 61% lower relative risk of unscheduled acute care use in the first 12 weeks (42.9% vs 70.3% for VEN+HMA; p<0.001). VEN schedule intensity was also captured, with only 22.8% receiving the full FDA-labeled 28 days of VEN during the 28-day cycles; 44.6% did not receive >11 days of VEN per cycle, raising concerns of clinical consequences. Median time from mIDH1 test to receipt of result was 7 days in both cohorts. Median time from diagnosis to start of treatment was 14 vs 20 days for IVO+HMA vs VEN+HMA. The biggest differential driver of regimen choice was favoring selection of VEN+HMA due to hospital protocol (30.7% vs 16.5%). Conclusions: In a large, balanced cohort of nearly 300 patients with ND mIDH1 AML ineligible for IC, patients treated with IVO+HMA had higher rates of CR and CR+CRi/p, achieved CR faster, and had longer EFS compared to those treated with VEN+HMA. Approximately half of patients receiving VEN were unable to receive >11-day schedules, potentially impacting the regimen's efficacy. Despite the reduced intensity of VEN relative to label, patients receiving VEN+HMA had higher early incidence of FN and greater overall need for unscheduled acute care. Wait time for mutational test results was 7 days, well within the 14- to 20-day median times to treatment. Based on the efficacy seen in this real-world assessment, consistent with the efficacy demonstrated in the AGILE clinical trial of IVO+azacitadine, clinicians and hospitals should ensure early mutational testing occurs, to enable consideration of IVO+azacitadine as the frontline treatment of choice for patients with ND mIDH1 AML.

GEM2017FIT Trial: Induction Therapy with Bortezomib-Melphalan and Prednisone (VMP) Followed By Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab (D), 18 Cycles, Followed By Consolidation and Maintenance Therapy with Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients Aged between 65 and 80 Years

Background: In transplant-ineligible patients (pts) with NDMM, VMP and Rd have been standards of care. The Spanish Myeloma Group examined induction with VMP followed by Rd, and results were particularly striking for “fit” pts aged 65-80 with a CR rate of 47% and an MRD negative rate (MRD(-)) of 20%. The median PFS was 34 months (m) and 4-years (yrs) OS rate was 70%. Pts and study design: Based on this background, we consider VMP9-Rd9 as control arm and compared with KRd or D-KRd. Induction included 18 cycles, followed by 4 D-Rd consolidation cycles for the two first arms (to evaluate if anti CD38 consolidation might compensate its absence as induction). Subsequently, pts were stratified by MRD (positive and negative) to maintenance therapy with D-R vs observation. Frailty was evaluated with Geriatric Assessment in Hematology (GAH scale) considering as fit those younger than 80 years and with a punctuation between 0 and 42. VMP and Rd were given at conventional doses and in the K-based regimens, K was given at dose of 36mg/m 2 twice weekly during C1-2 and at 56 mg/m 2 weekly since C3. R was given at standard dose and D was planned as IV but switched to SC, both at the conventional dose and schedule. The primary endpoint was to evaluate the MRD(-) rate (NGF 10 -5) at the end of induction to compare both experimental arms, KRd and D-KRd to the control-one, VMP-Rd. A step-down testing procedure was applied, whereby inference for a test in the pre-defined hierarchy was dependent upon statistical significance having been achieved for the previous tests in the hierarchy. No formal adjustment for multiplicity of contrasts is required. Secondary endpoints referred to the induction phase included the serological responses, PFS and OS probabilities at 18 cycles and safety profile. Results: 540 pts were screened and 78 were screening failures. 462 pts were randomized to VMP-Rd (154 pts), KRd (154 pts) and D-KRd (153 pts but one patient was not evaluable). Baseline characteristics of the pts were comparable in the three arms with a median age of 72 and around one third older than 75 years. Nearly one third of pts in the three arms had ISS 3 and 15% had extramedullary disease. A total of 369 out of 461 pts have completed the 18 induction cycles (128 in VMP-Rd, 122 in KRd and 119 in D-KRd) and were evaluable for the primary endpoint. The MRD(-) rate at 10 -5 was 32% for VMP-Rd, 69% for KRd (p<0.0001) and 79% for D-KRd (p<0.0001). At 10 -6, the MRD(-) rate was also significantly superior for KRd (59%) and D-KRd (75%) in comparison with VMP-Rd (24%) (p values <0.0001). The ORR at the end of induction was comparable in the three arms (87%, 89% and 89%, respectively) but the sCR/CR rate was significantly higher for KRd (59%) and D-KRd (61%) in comparison with VMP-Rd (40%) (p-values <0.0001). At 18 m, the proportion of pts alive and progression-free was 79% for VMP-Rd and 87% for KRd and D-KRd, respectively. Only two pts who achieved MRD negativity have progressed thus far. The OS at 18 m in the VMP-Rd, KRd and D-KRd arms was 91%, 95% and 90%, respectively. There were 48, 44 and 40 pts who early discontinued therapy in VMP-Rd, KRd and D-KRd, respectively, due to progressive disease (VMP-Rd: 23; KRd: 9;D-KRd: 6) or toxicity (VMP/Rd:8; KRd: 14; D-KRd: 6). Death occurred in 12 pts treated with D-KRd being infections the cause in 10 pts (Covid-19 in 3); 5 pts in the KRd arm (4 infections (Covid-19 in 1)) and 6 pts in VMP-Rd arm (infections in 4 pts). Concerning hematological toxicity during induction, G3/4 neutropenia was higher in VMP-Rd (50%) than KRd (24%) (p<0.0001) and similar to D-KRd (47%). G3/4 thrombocytopenia was also higher in VMP-Rd (34%) than the other two arms (16% and 17%, p<0.0001)). G3/4 infections rate was comparable in the three arms (12% in VMP-Rd and 15%-16% in KRd and D-KRd). Cardiovascular G3/4 events were higher in KRd (11%) and D-KRd (14%) than in VMP-Rd (5%) (p<0.0001) being hypertension and cardiac failure the most frequent-ones. Conclusions: The trial met its primary end point and the MRD(-) rates of 69% for KRd and 79% for D-KRd were significantly higher than VMP9-Rd9 (32%). Overall, the VMP-Rd arm had higher rates of neutropenia, while the D-KRd arm had higher rates of infections leading to death. The trial is ongoing to evaluate long term outcomes.

Early-Onset Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) without SF3B1 Mutations in Adults: Enrichment with Germline Variants in Genes Responsible for Congenital Sideroblastic Anemias

Introduction: Acquired mutations in SF3B1 gene in myeloid neoplasms are classically associated with the presence of RS in Pearl Stain, ineffective erythropoiesis, and favorable prognosis. Nevertheless, in up to 20-25% of adults diagnosed with MDS with RS (WHO 2017), mutations in SF3B1 are not found, and molecular grounds for the presence of RS remain to be ascertained. The objective of our study was to investigate whether the presence of RS could be associated with germline variants in genes responsible for congenital sideroblastic anemia (CSA). Methods: Patients diagnosed with de novo MDS between 16-60 years of age without previous organ dysfunction were recruited from 32 centers of GEMSD since 2016. Whole exomes were sequenced using HiSeq4000-NovaSeq6000-Illumina, paired tumor-germline samples. Mean depth was 100x, with 150 million reads per sample and quality Q30a>95%. Variants were analyzed using a bioinformatics pipeline: filtering intronic and synonymous variants and those with a population frequency >1%. The mutational state of SF3B1 was determined by Sanger Sequencing and Next Generation Sequencing (NGS). Germline variants were categorized according to American College of Molecular Genetics (ACMG) criteria. The list of genes related to CSA explored in this study is shown in Table 1. Results: Among 239 cases of adults diagnosed with early-onset MDS (mean age at diagnosis: 48 years, range 16-60), 58 (24%) patients presented with RS in bone marrow (mean RS: 28%). Of these 58 patients, acquired mutations in SF3B1 were not found in 32 (55%). Nine out of these 32 (25%) harbored a germline variant (two variants in one case) in genes responsible for CSA (Table 2): SLC25A38 (n=2), STEAP3 (n=2) FECH, ALAS2, GLRX5, SLC19A2, TRNT1 and IARS2. This frequency was statistically higher than in the SF3B1 and RS mutated group (n=23), with only one case with a germline variant in a CSA gene (p=0.013). It was also higher than in the non-RS cases (n=181), with only one case in this group (p<0.001). Using the Fisher's exact test, commonly used to perform enrichment, the odds ratios were also significant (p=0.033 and p<0.0001), respectively. Among patients with RS, those carrying a CSA gene germline variant were younger (43 vs. 54 years, p=0.04), had a higher rate of neutropenia (1.8 vs. 2.6 x 10E9/L, p=0.02), and thrombocytopenia (151 vs. 259 x 10E9/L, p=0.03) than MDS-RS patients with SF3B1 mutated. Furthermore, MDS-RS with a germline variant in CSA genes had a lower mean percentage of RS than patients who acquired the mutation in SF3B1 (14% vs. 38%; p=0.003). Conclusions: In our series, the frequency of MDS-RS without SF3B1 mutations is higher in early-onset adult MDS than the one reported in MDS in advanced age. Whole exome analysis allowed us to describe, for the first time, a significant enrichment of variants in genes causing CSA in young adults with RS and without acquired mutation in SF3B1.

Assessment of hospitalizations and cytopenia events among patients with extensive stage small cell lung cancer (ES-SCLC) receiving chemotherapy with trilaciclib.

531 Background: Prior studies have reported that that nearly 75% of patients receiving chemotherapy for small cell lung cancer present a hospitalization associated with myelosuppression. Trilaciclib is a myeloprotective agent indicated for use prior to chemotherapy in ES-SCLC. Given the relative recency in trilaciclib approval (2/12/2021), this study assessed real-world outcomes associated with trilaciclib among patients with ES-SCLC. Methods: This study was a retrospective analysis of adult ES-SCLC patients diagnosed between 2020 and 2023 using the 100% Medicare Fee-for-Service and MORE2 Registry claims databases. Eligible patients met literature-based criteria for ES-SCLC using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes, received platinum/etoposide- or topotecan-based chemotherapy regimens after diagnosis, and were continuously enrolled ≥ 30 days preceding and following chemotherapy initiation. Patients were categorized into 2 mutually exclusive cohorts: 1) trilaciclib administered at chemotherapy initiation and with no granulocyte colony stimulating factor (G-CSF) received during chemotherapy, and 2) no trilaciclib administered during chemotherapy. Chi-square tests and student’s t-tests were used to assess statistically significant differences between groups on cytopenia events (based on the appearance of an ICD-10 diagnosis code) and all-cause hospitalizations during the post-index period. Data use agreements prohibit reporting of categorical outcomes of < 11 patients. Results: 132 trilaciclib (mean age 70.6, male 50.8%) and 12,305 non-trilaciclib patients (age 68.0, male 48.2%) were eligible for the study; median follow-up was 202 days. Compared to the non-trilaciclib cohort, patients receiving trilaciclib had a lower rate of hospitalizations per patient per month during follow-up (0.14±0.25 vs. 0.19±0.27; p <0.001). Within 90 days post-chemotherapy initiation, trilaciclib was associated with lower rates of hospitalization (21.2% vs. 32.4%; p <0.01) and febrile neutropenia (< 3% vs. 5.7%, p=0.01). Anemia (44.7% vs. 52.6%, p=0.07), neutropenia (9.1% vs. 14.9%, p=0.06) and thrombocytopenia (5.3% vs. 8.4%, p=0.2) were numerically lower for trilaciclib patients in the 90-day post-index period. Results were similar when the non-trilaciclib group was stratified by prophylactic G-CSF usage. Conclusions: This real-world study demonstrated that receiving trilaciclib prior to chemotherapy treatment was associated with a lower rates of hospitalizations and cytopenia events, suggesting trilaciclib may prevent adverse events associated with treatment for ES-SCLC.

Investigation and analysis of occupational hazard factors in different industries in Tongliao City

Objective: To investigate the occupational hazard factors of different industries in Tongliao City, and to provide scientific basis for the prevention and control of occupational disease in Tongliao City. Methods: In July 2021, the detection data of coal dust, silica dust, cement dust, benzene, noise and other occupational hazard factors, as well as the occupational health examination data of workers in various positions of 104 enterprises in different industries in Tongliao City were cllected and anylazed. χ(2) test was used to analyze the results of chest radiography of workers in different age groups. Results: A total of 104 enterprises were investigated, and the median time-weighted average concentration (C(TWA)) of coal dust, silic a dust, cement dust and benzene in contact with test posts were 0.94, 0.30, 0.70 and 0.95 mg/m(3), respectively. The median 8 h equivalent sound level (L(EX, 8 h)) of noise was 74.1 dB (A) . The over standard rates of silica dust, cement dust and noise contact positions were 10.83% (16/240) , 7.14% (2/28) and 0.48% (3/628) , respectively. The differences of chest X-ray examination of coal dust and silica dust workers in different working ages were statistically significant (χ(2)=218.50, 531.80, P<0.001) . The difference of hearing threshold of noise workers with different working age was statistically significant (χ(2)=1290.00, P<0.001) . The rates of leukopenia and neutropenia were 41.90% (44/105) and 20.95% (22/105) in benzene exposed workers. The positive rate of brucella exposure workers was 1.33% (1/75) for tiger red plate agglutination test and 3.23% (3/93) for tube agglutination test. Conclusion: Silica dust, cement dust and noise exceed the standard in some posts and places in the Tongliao City, and some workers are infected with Brucella. In the future, we can focus on monitoring noise-generating posts, strengthen supervision and implement prevention and control measures to reduce the incidence of occupational diseases.

Platelet count and dose, but not comorbidities, predict severe neutropenia in cabazitaxel-treated prostate cancer patients: Aretrospective observational study.

To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n=19), followed by dyslipidemia (n=14) and diabetes (n=11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels <22.4×104/μL and those receiving cabazitaxel doses >34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

Impact of BMI in Patients With Early Hormone Receptor-Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial.

BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.

Safety and efficacy of preoperative chemotherapy for muscle-invasive bladder cancer in elderly patients.

This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.

A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer

IntroductionAbiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. Patients and MethodsThe medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. ResultsA total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. ConclusionIn Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates.

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44-2.88], p < 0.001; HRIndian:1.88 [1.11-3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07-1.54], p = 0.006; HRIndian:1.50 [1.19-1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

High levels of NK Cells in graft are associated with reduced febrile neutropenia after haploidentical peripheral blood stem cell transplantation.

To investigate the impact of natural killer (NK) cells in the graft on the outcome following haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). We retrospectively collected data from patients who had undergone haplo-PBSCT at our centre from January 2019 to November 2021. The percentage of NK cells in stem cell grafts was detected by flow cytometry. Based on the median (range) count of NK cells (1.8 [0.4-6.0] × 108/kg), patients were separated into high and low NK cell count groups. Data from 96 patients were analysed. Patients were evenly distributed (48 in each group) into high and low NK cell count groups. There was no significant difference in neutrophil and platelet recovery between the two groups. However, the rates of febrile neutropenia, bacterial infection, and invasive fungal disease (IFD) were significantly reduced in the high compared with the low NK cell count group. There was no significant difference in rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections between groups. There was no significant difference between groups in grades II and above acute graft versus host disease (GVHD), progression-free survival (PFS), or overall survival (OS). A high number of NK cells in the graft may reduce febrile neutropenia, IFD and bacterial infection following haplo-PBSCT but it has no significant effect on aGVHD, PFS, or OS.

Rituximab versus obinutuzumab-based first-line chemoimmunotherapy for follicular lymphoma-a real-world multicenter retrospective cohort study.

The GALLIUM study showed a progression-free survival advantage of 7% in favor of obinutuzumab vs. rituximab-based immunochemotherapies as first-line therapy in follicular lymphoma (FL) patients. Yet, the toxicity appears to be increased with obinutuzumab-based therapy. This is a multicenter retrospective-cohort study including adult FL patients comparing the toxicity of first-line rituximab vs. obinutuzumab-based chemo-immunotherapies (R and O groups, respectively). We compared the best standard-of-care therapy used per time period, before and after obinutuzumab approval. The primary outcome was any infection during induction and 6months post-induction. Secondary outcomes included rates of febrile neutropenia, severe and fatal infections, other adverse events, and all-cause mortality. Outcomes were compared between groups.A total of 156 patients were included in the analysis, 78 patients per group. Most patients received bendamustine (59%) or CHOP (31.4%) as adjacent chemotherapy. Half of the patients received growth-factor prophylaxis. Overall, 69 patients (44.2%) experienced infections, and a total of 106 infectious episodes were recorded. Patients in the R and O groups had similar rates of any infection (44.8% and 43.5%, p = 1), severe infections (43.3% vs. 47.8%, p = 0.844), febrile neutropenia (15% vs. 19.6%, p = 0.606), and treatment discontinuation, as well as similar types of infections. No covariate was associated with infection in multivariable analysis. No statistically significant difference was evident in adverse events of grades 3-5 (76.9% vs. 82%, p = 0.427). To conclude, in this largest real-life study of first-line treated FL patients comparing R- to O-based therapy, we did not observe any difference in toxicity during the induction and 6months post-induction period.

Oral paclitaxel and dostarlimab with or without trastuzumab in early-stage, high-risk breast cancer: Results from the neoadjuvant ISPY 2 TRIAL.

LBA612 Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes including MammaPrint (MP) status to evaluate novel neoadjuvant agents in high-risk breast cancer. The primary endpoint is pathologic complete response (pCR). Oral Paclitaxel and encequidar (OPE) is an oral combination of paclitaxel (P) with a p-glycoprotein pump inhibitor, encequidar. Dostarlimab (D) is an intravenous (IV) PD-1 inhibitor. Methods: Women with tumors ≥ 2.5cm and MP high risk cancers (MP1 = MP high; MP2 = MP ultra-high) were treated starting Oct 5, 2020. Treatment included OPE (Oral P 205mg/m2 + encequidar 12.9mg) on days 1-3 weekly x 12 and D 500 mg IV given q 3 weeks x 4, followed by doxorubicin/cyclophosphamide (AC) q 2-3 weeks x 4. Patients with HER2+ disease received IV weekly trastuzumab (T) during the first 12 weeks. The control arm was weekly IV P x 12 with or without trastuzumab followed by AC q 2-3 weeks x 4. OPE + D was eligible to graduate [85% chance of success in a 300-person phase 3 neoadjuvant trial with a pCR endpoint] in any of the pre-defined signatures. Results: 113 (78 HR+HER2-, 17 HR-HER2- and 18 HER2+ patients) received OPE + D +/- T. The control arm included 388 historical controls (201 HR+Her2-, 156 HR-HER2-, 31 HER2+). 77 patients (70 HR+ and 7 HR-) were MP1 and 36 patients (24 HR+ and 12 HR-) were MP2. Safety events of note for OPE + D versus IV P include increased rates of nausea (85% vs. 72%) diarrhea (77% vs. 41%). There was no significant difference in rates of neutropenia (23% vs.17%). Peripheral neuropathy (37% vs. 64%) and alopecia (59% vs. 66%) were significantly decreased. Immune related adverse events (irAEs) were lower than expected. Conclusions: Although both OPE and D have both been shown to have efficacy in other settings, combination therapy with OPE + D did not graduate in any of the predefined subtypes. In the HR+ signature where we would not expect a benefit of D, we see equal response to OPE with decreased rates of peripheral neuropathy and alopecia, which suggest this oral agent may be an attractive alternative to IV P in this subgroup and is under consideration in ISPY 2.2. We did not observe the expected improvement in pCR rates seen with PD-1 inhibitors in the HR- or MP2 subtypes (over P alone historic control). In addition, the irAEs were less than expected. Together these findings suggest interference of OPE with D. A potential mechanism of interference could be change in microbiome with the use of OPE vs. IV P, as the microbiome is known to influence the efficacy of immunotherapy. The source of interference is being investigated. Clinical trial information: NCT01042379 . [Table: see text]

SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL).

LBA4 Background: The addition of BV to initial chemotherapy improves overall survival (OS) in adults and PFS in pediatric patients (pts) with AS HL. However, frontline BV adds toxicity, most pediatric pts receive radiation therapy (RT), and 7-20% of pts still develop relapsed/refractory (RR) HL. The PD-1 pathway is central to the pathogenesis of HL and PD-1 blockade is effective in RR HL. The adult and pediatric cooperative groups of the National Clinical Trials Network (NCTN) conducted the randomized, phase 3 S1826 trial to evaluate N-AVD vs BV-AVD in pts with newly diagnosed AS HL. Methods: Eligible pts were ≥12 years (y) with stage 3-4 HL. Pts were randomized 1:1 to either 6 cycles of N-AVD or BV-AVD. Recipients of BV-AVD were required to receive G-CSF neutropenia prophylaxis vs optional with N-AVD. Pre-specified pts could receive RT to residually metabolically active lesions on end of treatment PET. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. Response and disease progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was PFS; secondary endpoints included OS, event-free survival, patient-reported outcomes (PROs), and safety. Results: 994 pts were enrolled from 7/9/19 to 10/5/22; 976 were eligible and randomized to N-AVD (n=489) or BV-AVD (n=487). Median age was 27y (range, 12-83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were &lt; 18y, 10% were &gt; 60y, and 32% had IPS 4-7. So far, &lt; 1% of pts received RT. At the planned 2nd interim analysis (50% of total PFS events) the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary. 30 PFS events occurred after N-AVD vs 58 events after BV-AVD. With a median follow-up of 12.1 months, PFS was superior in the N-AVD arm [HR 0.48, 99% CI 0.27-0.87, one-sided p=0.0005); 1y PFS: N-AVD, 94%, BV-AVD, 86%. 11 deaths (7 due to adverse events, AE) were observed after BV-AVD compared to 4 after N-AVD (3 due to AE). The rate of grade (gr) ≥ 3 hematologic AE was 48.4% (45.1% gr ≥ 3 neutropenia) after N-AVD compared to 30.5% (23.9% gr ≥ 3 neutropenia) after BV-AVD. Rates (any gr) of febrile neutropenia (5.6% N vs 6.4% BV), pneumonitis (2.0% N vs 3.2% BV), ALT elevation (30.7% N vs 39.8% BV), and colitis (1% N vs 1.3% BV) were similar. Hypo/hyperthyroidism was more frequent after N-AVD (7%/3% N vs &lt;1% BV) while peripheral neuropathy (any gr) was more common after BV-AVD (sensory: 28.1% N vs 54.2% BV; motor: 4% N vs 6.8% BV). Conclusions: N-AVD improved PFS vs BV-AVD in pts with AS HL. Few immune AEs were observed and &lt; 1% of pts received RT. Longer follow-up is needed to assess OS and PROs. S1826, the largest HL study in NCTN history, is a key step towards harmonizing the pediatric and adult treatment of AS HL. Funding provided by: National Cancer Institute of the National Institutes of Health U10CA180888 and U10CA180819 and Bristol-Myers Squibb. Clinical trial information: NCT03907488 .

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression. To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor. Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022). Participants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos. The primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome. Among 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n = 289) was noninferior to valganciclovir (n = 297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference -1.4% [95% CI, -6.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0/52) who received letermovir and 12.1% (8/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, -37.9% [95% CI, -45.1% to -30.3%]; P < .001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%). Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication. ClinicalTrials.gov Identifier: NCT03443869; EudraCT: 2017-001055-30.

Prevention of chemotherapy-induced neutropenia (CIN) with plinabulin (Plin) vs placebo (Plac) in patients (pts) with non-small cell lung cancer (NSCLC) treated with docetaxel (Doc): A pooled analysis from 3 randomized trials.

e21163 Background: CIN can lead to increased patient/healthcare burden, resource utilization, hospitalizations, and poorer quality of life (QoL). G-CSF has a high incidence of bone pain and mild thrombopenia and is given the day after chemo. Plin, a novel non-G-CSF small molecule, protects the bone marrow stem cell, has minimal bone pain, and protects platelet precursors. Plin is given on the same day as chemo and has NSCLC anticancer efficacy (ESMO 2021, Feinstein). The CIN effects of Doc plus Plin vs Doc with Plac were pooled from 3 NSCLC clinical trials. Methods: Data from randomized trials, phase (Ph) 3 trial 103 (NCT02504489), Ph2/3 trial 105 ( NCT03102606 ), and Ph2 trial 101 (NCT00630110) were pooled. Pts were randomized to either Doc (75mg/m2) plus Plin (20mg/m2 or its pharmacokinetic equivalent) (n = 146) or Doc plus Plac (n = 296). Doc was administered on day 1 of each 21-day cycle x 4 cycles, and Plin or Plac was administered ~30 minutes after Doc. Neutrophil counts were taken at predose and day (D) 8 of each cycle in studies 101 &amp; 103, and on predose, D1, 2, 6, 7, 8, 9, 10, 15, and 21 in study 105. Pts given G-CSF in D1-D3 were excluded. Duration of severe neutropenia (DSN) was calculated by methods previously reported (ASH 2022, Blayney). All Grade (Gr) and Gr4 neutropenia (N) rates, Absolute N count (ANC), febrile N (FN) rate, and ANC on D8 (‘nadir’) were obtained. QoL scores were obtained in studies 103 and 105 by EORTC QLQ-C30. Patient-reported adverse events (AEs) were collected. Results: Pt demographics were comparable. Plin was statistically and clinically significantly superior to Plac for All Gr and Gr4 N frequencies, Day 8 ANC (‘nadir’), and DSN (all had p &lt; 0.0001). Febrile Neutropenia (FN) and infection rates were numerically lower (see table). Fewer pts were treated with antibiotics among pts treated with Plin. Platelet count was unaffected with Plin; grade (gr) 3/4 thrombocytopenia was &lt; 1% with either Plin or Plac. The total frequency of treatment-emergent AEs for Plin vs Plac were 71% vs 80%. QoL scores were similar for Plin and Plac. Conclusions: In 3 independent randomized studies (101, 103, and 105), Plin demonstrated a superior benefit for CIN and showed clinical benefit for infection rate versus Plac. Additionally, Plin has the added benefits of pt convenience (same-day dosing and no additional visits or wearable device), a favorable safety and tolerability profile, anticancer efficacy, and QoL maintenance, which represents a distinct advantage over G-CSF. Clinical trial information: NCT02504489 ; NCT03102606 ; NCT00630110 . [Table: see text]

Impact of SARS-COV2 infection on the clinical outcomes in patients with lung cancer.

e20572 Background: The outbreak of 2019 Novel coronavirus disease (COVID-19) has led to various deleterious outcomes in cancer patients. Those with lung cancer would be more susceptible to increased morbidity and mortality. We aimed to study the outcomes of COVID infection in patients with lung cancer. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database-2020 was queried to identify all admissions with COVID in patients with and without lung cancer. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of thrombocytopenia (TCP), Acute Respiratory Failure (ARF), sepsis, anemia, pancytopenia and shock. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 4,625 COVID admissions occurred in patients with lung cancer. Among them 71% (N = 3,288) were white, 17% (N = 805) were African American (AA) and 6.7% (N = 310) were Hispanic (HISP). Lung cancer patients had higher rates of smoking heart failure, CKD, CAD, COPD and anemia (p &lt; 0.01) and lower rates of DM and obesity (p &lt; 0.01). Lung cancer patients were more likely to have Medicare and less likely to have private insurance and were older (mean age 64.7 vs 71.9, p &lt; 0.01). On multivariate regression, after adjusting for confounders those with lung cancer had higher odds of all-cause mortality (aOR 1.41; 95% CI 1.18-1.70 ,p = &lt; 0.001). Among lung cancer patients, mean LOS was lower by 1 day (95% CI -1.4 to -0.4, p &lt; 0.001) and THC was also lower (-$16,672; 95% CI -22950 to -10393, p &lt; 0.001). Among the secondary outcomes, lung cancer patients had higher rates of pancytopenia (7.46% vs 1.59%, p &lt; 0.001), neutropenia (3.46% vs 0.68%, p &lt; 0.001) and venous thromboembolism (8.97% vs 4.29%, p = 0.006). Conclusions: COVID-19 infection led to increased mortality in lung cancer patients compared to those without lung cancer. This explains the overwhelming impact the pandemic left on lung cancer patients. The LOS and THC was decreased for lung cancer patients which may be explained by early death compared to non-lung cancer cohort. This study highlights the importance of decreasing the risk factors for COVID infection among lung cancer patients, including encouraging vaccination.

NALIRIFOX vs FOLFIRINOX vs gemcitabine plus nab-paclitaxel as first-line treatment of advanced pancreatic cancer: An individual patient data pooled analysis of phase 3 registration trials.

e16262 Background: The NAPOLI-3 trial showed the superiority of the NALIRIFOX regimen over the combination of gemcitabine and nab-Paclitaxel (GemNabP) as first-line treatment (1LTx) of advanced pancreatic cancer (PDAC), thus being candidate as a reference regimen in this setting. However, a comparison with the FOLFIRINOX regimen has not yet been performed. Methods: We performed a pooled analysis of phase III trials that defined FOLFIRINOX, NALIRIFOX and GemNabP as optimal 1LTx options in advanced PDAC. Individual patient outcomes were retrieved from Kaplan Meier plots of each trial, and analysed after assessment of data reconstruction accuracy. Progression free survival (PFS) and overall survival (OS) were compared between the three different arms, using Cox proportional hazard models including each trial as a random effect variable to account for inter-trial variability. Overall response rates (ORR) and Grade 3 or 4 (G3/4) toxicity rates were also compared. Results: A total of 1372 patients treated with FOLFIRINOX (n=171, 12), NALIRIFOX (n=383, 28) and GemNabP (n=818, 60) were included. Median PFS was significantly longer in patients treated with NALIRIFOX (7.4 months) as compared to FOLFIRINOX [6.4 months, HR 1.48 (95% CI 1.21 - 1.82), p&lt;.001] and GemNabP [5.6 months, HR 1.45 (95% CI 1.24 - 1.70), p = p&lt;.001]. NALIRIFOX also provided significantly higher ORR [42% vs 32% (FOLFIRINOX) vs 29% (GemNabP), p&lt;.001]. GemNabP was associated with poorer OS [9.2 months, HR 1.25 (95% CI 1.07 - 1.46), p=0.005], while no significant difference was observed between FOLFIRINOX [11.1 months, HR 1.12, (95% CI 0.88 - 1.43), p=0.344] and NALIRIFOX (11.1 months). Among G3/4 events, NALIRIFOX was associated with higher rates of diarrhea [p&lt;.001] and lower rates of peripheral neuropathy, thrombocytopenia and neutropenia [p&lt;.001], though with no difference in febrile neutropenia occurrence [p=0.158]. Conclusions: NALIRIFOX may provide superior ORR and PFS as compared to FOLFIRINOX and GemNabP as 1LTx of advanced PDAC, though with higher gastrointestinal toxicities and no difference in OS compared to FOLFIRINOX. Careful patient selection, drug costs consideration and direct comparison between FOLFIRINOX and NALIRIFOX is warranted. [Table: see text]

A phase 1b study to evaluate the efficacy, safety, and pharmacokinetics of an investigational microbiome therapeutic, SER-155, in adults undergoing hematopoietic stem cell transplantation.

TPS7080 Background: In patients undergoing allogeneic hematopoietic cell transplantation (HCT), loss of gastrointestinal microbial diversity is associated with risk of bloodstream infections (BSI), acute graft-versus-host disease (aGvHD), and death. SER-155 is a rationally designed investigational cultivated microbiome therapeutic, hypothesized to improve clinical outcomes in HCT by restoring colonization resistance to potential pathogens, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a Phase 1b study evaluating the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT. Methods: This study will enroll approximately 70 subjects ≥18 years in an open-label Cohort 1 (n = 10) followed by a double-blind, placebo-controlled Cohort 2 (n = 60) randomized 1:1 to SER-155 or placebo. A variety of conditioning regimens, donor types, and GVHD-prophylaxis regimens are included. Exclusion criteria include history of severe colitis or active inflammatory bowel disease or total colectomy, umbilical cord blood or ex vivo T-cell depletion, exposure to fecal microbiota transplant or any live microbial therapeutic within 3 months prior to screening, and evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Following screening, participants in both cohorts receive 2 treatment courses (one before and one after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, plus a conditional 3rd treatment course if the subject receives antibiotics. Safety outcomes are followed through 52 weeks post HCT. The primary endpoint is the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include rates of BSI, gastrointestinal infections, aGvHD, febrile neutropenia and overall survival. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. Results: Cohort 1 enrollment is complete, with 13 participants receiving SER-155. In December 2022, the Data and Safety Monitoring Committee supported continuation to Cohort 2 enrollment following review of safety data from Cohort 1. Enrollment in Cohort 2 is underway. Conclusions: This Phase 1b study is designed to assess the safety, and clinical efficacy of SER-155 in allogeneic HCT, expanding the clinical experience of microbiome- directed interventions in allogeneic HCT recipients. Clinical trial information: NCT04995653 .

Safety of same day administration of pegfilgrastim in breast cancer patients.

e18850 Background: Myelosuppressive therapy plays a crucial role in the treatment plan of patients with cancer; one common toxicity associated with myelosuppressive regimens is neutropenic fever. Pegfilgrastim is approved for use no sooner than 24 hours after receiving cytotoxic therapy, based on the initial FDA indication, requiring a return to clinic or the use of a patented on-body injector placed at the time of treatment. However, alternative schedules assessing earlier administration were never examined in the FDA registration studies. Small studies have suggested that same-day administration of pegfilgrastim can be carried out safely, including a prior safety study at UAB. The present analysis sought to test the non-inferiority of same day pegfilgrastim compared to administration 24-72 hours after cytotoxic chemotherapy. Methods: We undertook a retrospective analysis of 241 breast cancer patients receiving cytotoxic therapy from May 2016 through October 2018. The patient population was predominately Caucasian women with 28% African American or Asian women, and a median age of 55 (33-81). I2B2 codes identified patients with breast cancer receiving adjuvant or neoadjuvant therapy patients receiving same day versus next day pegfilgrastim were compared. Blood counts, delays in therapy, and neutropenic hospitalizations were analyzed for same day versus 24-hour delayed pegfilgrastim at two separate institutions. Dose reduced metastatic regimens were excluded from this review. Results: We comparedthe rate of neutropenia resulting in dose-delay for breast cancer patients receiving standard chemotherapy with administration of pegfilgrastim on both schedules. Overall, neutropenia with fever resulting in delay of subsequent chemotherapy was similar in both groups with same day administration being non-inferior to the standard administration schedule. Other treatment delays due to non-neutropenic conditions included mucositis, port malfunction, COPD, fatigue, and transportation delays. Conclusions: Policies requiring 24-hour delays following chemotherapy for pegfilgrastrim administration, reduce utilization of biosimilars and make the on-body injector, Onpro, a more convenient, albeit expensive option, for patients and the health system. These data suggest that same day administration of pegfilgastrim are non-inferior to delayed administration and may provide both substantial cost savings and quality of life benefits to patients and health care systems by increasing utilization of biosimilars and removing the need for a return visit after chemotherapy. In addition, same day administration also reduces the risk of complications associated with on body injector use, where failure rates of up to 10% are reported.