Rate Of Febrile Neutropenia Research Articles

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.

Growth factor use in patients with breast cancer treated with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen: Cost implications in a safety-net system.

10 Background: Growth factor (G-CSF) support has been shown to reduce the incidence of neutropenic complications after chemotherapy; however, it can be associated with a significant increase in cost of care. Here, we reviewed G-CSF use in breast cancer patients receiving docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen at a safety-net system. Methods: Parkland Health is the safety-net system that provides care to primarily uninsured/underinsured patients in Dallas County, Texas. The majority of patients treated at Parkland belong to racial and ethnic minorities. We reviewed electronic medical records of patients with HER-2 positive breast cancer who were treated with TCHP between 01/01/2017 and 12/31/2022 at Parkland. Data on patient demographics, treatment history, laboratory values, and treatment related complications were collected. Results: A total of 171 consecutive patients underwent neoadjuvant/adjuvant treatment with TCHP for HER-2 positive breast cancer. Forty-one patients (24.0%) received G-CSF for primary prophylaxis, as per discretion of treating physician. In the 130 patients (76.0%) who did not receive primary prophylaxis, G-CSF was added later in 41 patients (32.5%). Febrile neutropenia (FN), neutropenic treatment delays, and infections not meeting FN criteria accounted for the majority of cases where G-CSF was added later in the course of treatment. Overall, 529 cycles of TCHP were administered without G-CSF vs. 372 cycles with G-CSF. Without primary prophylaxis, 18.5% (24/130) of the patients developed FN vs 2.4% (1/41) for those who received primary prophylaxis, p=0.011. FN was a complication in 4.5% (24/529) of chemotherapy cycles without G-CSF vs. 1.1% (4/372) of cycles administered with G-CSF, p=0.003. In patients treated without G-CSF, the majority of FN episodes (71%) occurred within the first 3 cycles. FN resulted in a total of 150 days (median 5 days) of hospital stay resulting in $1.2 million (M) in charges (median $36,000 per admission). Universal G-CSF use in our patient population could have prevented 21 episodes of febrile neutropenia with an estimated saving of $1.05 M (hospital admission charges), at an extra cost of $1.8M (based on the pegfilgrastim Medicare average sales price (ASP) from 2017-2022). However, based on the 2023 Medicare ASP, by substituting pegfilgrastim for biosimilars, the estimated cost would have been $603,000. Conclusions: Our study did not show an FN rate >20% to warrant routine addition of G-CSF for primary prophylaxis as recommended by the NCCN. During the study period, the cost of G-CSF was prohibitive for its universal use. However, the recent introduction of G-CSF biosimilars has significantly reduced the cost burden and justifies routine G-CSF prophylaxis as a cost saving measure.

Real-World Impact of Prophylactic Growth Factor Use on Timing of Febrile Neutropenia and Infection After High-Risk Chemotherapy.

Prophylactic growth-factor therapy with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients with breast cancer initiating myelosuppressive chemotherapy. However, little is known about the protective benefit early in the chemotherapy cycle. To assess the relationship between G-CSF prophylaxis and incidence of FN/infection in week 1 versus beyond week 1 of the first chemotherapy cycle, a retrospective study was conducted using Medicare claims from 2005 through 2020 among patients with breast cancer initiating high-risk chemotherapy. Two cohorts were compared based on G-CSF prophylaxis within 3 days following chemotherapy initiation. The primary outcome was FN or infection, defined as hospitalization with neutropenia, fever, or infection diagnosis. Secondary outcomes were a stricter definition of FN and infection-related hospitalization. Unadjusted and regression-adjusted proportions of patients experiencing each outcome during week 1 versus beyond week 1 of the first chemotherapy cycle were compared. Of 78,810 patients meeting all inclusion criteria (>98% female; mean age, 69 years), 79% initiated TC (docetaxel/cyclophosphamide), 14% TCH (docetaxel/carboplatin/trastuzumab), and 7% TAC (docetaxel/doxorubicin/cyclophosphamide). Among patients receiving G-CSF (74%), incidence of first-cycle FN/infection was lower compared with patients not receiving G-CSF (overall, 6% vs 13%; TAC, 12% vs 19%; TC, 6% vs 12%; TCH, 5% vs 15%). However, patients who received G-CSF were generally more likely to experience FN/infection in week 1 (adjusted odds ratio [aOR], 1.24 for all; 1.73 for TAC; 1.35 for TC; and 0.76 for TCH). Results were similar for strictly defined FN (overall aOR, 1.29 for week 1 and 0.12 for beyond week 1) and infection-related hospitalization (overall aOR, 1.33 for week 1 and 0.27 for beyond week 1). Overall, the rates of chemotherapy-related FN and infection in week 1 of the first chemotherapy cycle are similar for patients receiving and not receiving G-CSF, suggesting continued risk in week 1 despite prophylactic G-CSF.

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.

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 .

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 .

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]

Poor Renal Function and a High Modified Glasgow Prognostic Score Are Predictive Factors for Nedaplatin/5-Fluorouracil Combination Therapy-induced Febrile Neutropenia.

Nedaplatin (NDP)/5-fluorouracil (5-FU) combination therapy frequently causes severe neutropenia and febrile neutropenia (FN). However, there is no consensus on the risk factors for FN caused by NDP/5-FU combination therapy. Mouse models of cancer cachexia are known to be susceptible to infections. Conversely, the modified Glasgow prognostic score (mGPS) is believed to reflect cancer cachexia. We hypothesized that mGPS is a predictive factor for FN caused by NDP/5-FU combination therapy. We analyzed the relationship between mGPS and FN in patients who received NDP/5-FU combination therapy at Nagasaki University Hospital using multivariate logistic analysis. In total, 157 patients were studied, 20 of whom developed FN (12.7%). Multivariate analysis revealed that mGPS 1-2 [odds ratio (OR)=4.13, 95% confidence interval (CI)=1.42-12.02, p=0.009] and creatinine clearance <54.4 ml/min (OR=5.81, 95% CI=1.81-18.59, p=0.003) were significantly associated with the development of FN. Several guidelines suggest that patients receiving chemotherapy with an FN rate 10-20% should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF), depending on the individual patient's risk of developing FN. When NDP/5-FU combination therapy is administered to patients with risk factors identified in this study, prophylactic administration of G-CSF should be considered. In addition, the neutrophil count and axillary temperature should be monitored more frequently.

A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future.

115 Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Methods: We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Results: Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1*10*9/L vs 2.90*10*9/L, p&lt;0.0001); and neutropenia rates were markedly lower (2% vs. 93%, P=&lt;0.0001). Hospital admission rates were significantly lower in G-CSF users compared to non-users (19% vs. 69%, P&lt;0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusions: During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.

Does ferritin level affect the outcomes of autologous stem cell transplantation equally in all diseases?

BackgroundIn this retrospective study, we evaluated the effect of ferritin levels on the outcomes of autologous stem cell transplantation in patients with MM or lymphoma. MethodsIn this study, 170 patients with measured ferritin levels within one month before transplantation who underwent ASCT with the diagnosis of MM or lymphoma were evaluated. The cut-off value of ferritin was determined as 500 ng/mL to evaluate the transplant outcomes in both groups. The hematological recovery status/duration, febrile neutropenia rate, hospitalization time, transplant-related mortality (TRM) in the first 100 days, and OS were evaluated according to the ferritin level ResultsOf all patients, 105 (61,8%) were diagnosed with MM and 65 (38.2%) with lymphoma. Ferritin levels had no statistically significant effect on the engraftment status/times, the febrile neutropenia rates, and hospitalization times of both lymphoma and myeloma patients (p > .05). Ferritin level was not significantly associated with TRM in MM (p = .224). However, in lymphoma, ferritin level was significantly associated with TRM (33.3% for ferritin level ≥500 ng/L vs. 5.3% for ferritin level ng/mL, p = .005). There was no statistically significant correlation between ferritin value and OS in MM group [ferritin level ≥ 500 ng/L: 39.9 months (95% CI: 33.7–46.1) and ferritin level 500 ng/mL: 39.4 months (95% CI: 36.5–42.2), p = .446]. Ferritin level was significantly associated with OS in patients with lymphoma [ferritin level ≥ 500 ng/L: 22.1 months 95% CI: 14.7–29.5), ferritin level 500 ng/mL: 27.3 months (95% CI: 22.4–32.2), p = .038] ConclusionHigh ferritin level is important prognostic factor on survival after ASCT in patients with lymphoma.

Pegfilgrastim on febrile neutropenia in pediatric and adolescent cancer patients: a systematic review and meta-analysis

ABSTRACTObjectivesThere is no meta-analysis about the effects of pegfilgrastim on the occurrence of febrile neutropenia (FN) in pediatric/adolescent cancer patients. The study explored the efficacy of prophylactic pegfilgrastim in preventing FN in children/adolescents with cancer.MethodsPubMed, Embase, and the Cochrane Library were searched for studies published before April 7, 2020. The primary outcome was the rate of FN. Effect size (ES) and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the outcome. The ES represented the rate of FN, and the STATA ‘metaprop’ command was used to synthesize the rate.ResultsEight studies were included, comprising 167 patients and 550 courses of treatment. There was no difference between pegfilgrastim and filgrastim for the rate of FN in children receiving chemotherapy (OR = 0.68, 95% CI: 0.20–2.23, P = 0.520). In patients receiving pegfilgrastim, the rate of FN was 25.6% (95% CI: 14.9%−36.3%), the rate of grade 4 FN was 38.3% (95% CI: 19.2%−59.5%), the rate of severe neutropenia (SN) was 40.5% (95% CI: 35.1%−46.1%), and the rate of treatment delays due to FN was 4.8% (95% CI: 0.8%−11.3%).DiscussionThe number of studies that could be included was small; therefore, a specific type of cancer or a specific treatment could be studied. Heterogeneity was high.ConclusionThere was no difference between pegfilgrastim and filgrastim for the rate of FN. The use of pegfilgrastim was still associated with rates of FN, grade 4 FN, severe neutropenia, and treatment delays due to FN in pediatric cancer patients.

Influence of a biliary stent in patients with advanced pancreatic cancer treated with modified FOLFIRINOX.

Endoscopic biliary drainage is the recommended 1st-line treatment for malignant biliary obstruction. Although a high incidence of febrile neutropenia has been reported in patients treated with FOLFIRINOX and a biliary stent, it remains unknown whether the biliary stent contributes to patient survival. Thus, we aimed to elucidate the effects of biliary stents on the survival of patients with advanced pancreatic cancer treated with modified FOLFIRINOX (mFFX). We retrospectively reviewed medical charts of patients with advanced pancreatic cancer treated with mFFX between January 2014 and April 2020. We compared the overall survival (OS) of patients with and without biliary stent during mFFX treatment and examined the independent effect on mortality using propensity score matching. Overall, we included 89 patients (stent group, n = 24; non-stent group, n = 65). The proportion of patients with pancreatic head cancer was significantly higher in the stent group than in the non-stent group (P < .01). Stratification analysis in patients with pancreatic head cancer revealed that OS was significantly shorter in the stent group than in the non-stent group (P = .03). After propensity score matching, 19 pairs of patients in each group were analyzed. The stent group revealed a significantly shorter survival than the non-stent group (median OS, 10.3 vs 24.9 months; P < .01). The incidences of febrile neutropenia (P = .01) and biliary tract-related events that required biliary stenting or stent replacement (P < .01) were significantly higher in the stent group than in the non-stent group. Stent insertion was an independent risk factor for overall mortality. Biliary stents may reduce survival in patients with advanced pancreatic cancer. The rate of febrile neutropenia was higher in the stent group than in the non-stent group. There is a need to assess the patient's condition with discretion and develop a treatment strategy with short prognosis in mind after stent insertion.

Venetoclax in Combination with Hypomethylating Agents Compared to Standard Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia

Introduction: The safety and efficacy of venetoclax (VEN) in combination with hypomethylating agents (HMA) in older adults with newly diagnosed acute myeloid leukemia (AML) or those ineligible for intensive chemotherapy is well established. Recently, VEN/HMA has emerged as a potential option in relapsed or refractory (r/r) AML. Although encouraging, data on whether this combination compares favorably to standard chemotherapy (SC) in r/r AML are limited. Methods: This was a single-center, retrospective analysis from November 2012 to March 2022 that compared VEN/HMA to SC in r/r AML patients at a 923-bed tertiary care hospital with an outpatient cancer facility. The primary endpoint was overall response rate (ORR) defined as rate of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphological leukemia-free state (MLFS), and partial remission (PR). Key secondary outcomes included overall survival (OS), relapse-free survival (RFS), and toxicity. Continuous variables were compared using the Mann-Whitney U test or the two-sample t-test and categorical variables were compared using the Chi-squared or Fisher's exact test. Time to event data were assessed using the Kaplan-Meier method. Log-rank test was used to compare the survival endpoints between groups. A p-value < 0.05 was considered statistically significant. Results: A total of 281 patients underwent screening, of those, 63 adult patients were included in the analysis (VEN/HMA, n = 25 and SC, n = 38). The primary reason for exclusion was previously untreated AML or myelodysplastic syndrome. Baseline characteristics were balanced between the groups. Overall, 53 patients had de novo AML, 25 patients had received 3 or more prior lines of chemotherapy, 20 patients were ≥ 60 years, and 8 patients had undergone previous stem cell transplantation. In the VEN/HMA cohort, 32% had prior exposure to a hypomethylating agent and 36% received concomitant azole antifungals. The majority of patients in both groups were stratified as intermediate or poor risk according to the European LeukemiaNet (ELN) 2017 criteria. Common chemotherapy regimens included MEC (74%), ME (12%), and FLAG ± IDA (11%). Most patients in the VEN/HMA group received decitabine and of those, 60% initiated therapy in the outpatient setting. Treatment outcomes are shown in Table 1 and OS results are presented in Figure 1. Both therapies resulted in similar ORRs (VEN/HMA 52% vs SC 42%, p=0.44). Combined CR/CRi was achieved in 36% of patients in the VEN/HMA group and 37% of patients in the SC arm (p=0.95). Median time to response was 73 days for VEN/HMA and 45 days for SC (p=0.38). The OS between VEN/HMA and SC groups was not statistically different (p=0.99, log-rank test) with median OS of 287 days and 285 days, respectively. No difference in RFS was observed between the two groups (0.38, long-rank test) with median RFS of 304 days in the VEN/HMA arm and 325 days in SC group. Prior HMA exposure in VEN-treated patients was associated with a lower CR/CRi rate (13% vs 41%, p=0.09). Induction mortality rates at 30 and 60 days were similar between the groups. Duration of hospitalization was significantly shorter in patients who received VEN/HMA as compared to those who received SC (p=0.04). In terms of safety, patients treated with VEN/HMA had lower rates of any grade diarrhea (40% vs 71%, p=0.01), any grade mucositis (20% vs 61%, p=0.001), and grade ≥ 3 anemia (80% vs 97%, p=0.02). The rate of febrile neutropenia was significantly higher in the SC group than in the VEN/HMA group (97% vs 40%, p<0.00001), as was the rate of bacterial infections (50% vs 24%, p=0.03). Fungal pneumonias were also reported more frequently in patients receiving SC (37% vs 12%, p=0.04). Lastly, a trend toward a longer median time to platelet recovery was noted in VEN/HMA patients receiving concomitant azole antifungals (38 days vs 26 days, p=0.52). Conclusion: Treatment with VEN/HMA yielded similar outcomes compared with SC and was associated with lower infection rates, a potential advantage in a patient population at high risk for infectious complications. Additionally, safe initiation of this regimen in the outpatient setting and shorter duration of hospitalization when compared to SC could lead to a reduction in use of healthcare resources and improvement in quality of life. These findings add to a growing body of evidence that suggest VEN/HMA is non-inferior to SC with a favorable toxicity profile. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real World Effectiveness of "7 + 3" Intensive Chemotherapy Vs Venetoclax and Hypomethylating Agent for Initial Therapy in Adult Acute Myeloid Leukemia

Introduction Initial treatment selection for older adults with AML remains challenging. Historically, clinicians and patients had to choose between intensive chemotherapy (7 + 3), low intensity therapy or best supportive care. Approval of venetoclax and a hypomethylating agent (ven/HMA, NCT02993523) for those ≥75 years or with major comorbidities has offered higher response rates and improved survival vs. low intensity therapy. Use has expanded to other groups like younger patients with high risk disease or patients with "borderline" induction fitness. Prospective comparisons have yet to complete, so we examined retrospective outcomes for older patients receiving either 7 + 3 or ven/HMA as initial therapy. Methods We included patients from both the University of Pennsylvania ("HUP", n=187) and the Flatiron Health electronic health record derived, de-identified database with incident AML diagnosed between January 2017 and 2021, and 7 + 3 (7 days of cytarabine and 3 days of anthracycline) or ven/HMA (azacitadine or decitabine) as initial therapy (n=621). Only patients presumably eligible for 7 + 3 were included (age 60-75, estimated glomerular filtration rate > 30 mL/min, alanine transaminase, aspartate transaminase, bilirubin < 1.5x upper limit of normal (ULN), no history of systolic heart failure). Primary endpoint of overall survival (OS) had 80% power for hazard ratio (HR) 0.74 with alpha 0.05. OS was analyzed by Kaplan-Meier method and compared using log-rank test. Pre-planned sensitivity analyses included multiple imputation (MI) with inverse-probability of treatment weighting (IPTW) to address missingness and balance baseline covariates. Results 305 patients received 7 + 3 and 503 received ven/HMA. Baseline covariates showed ven/HMA patients were older, sicker and had worse disease biology (table 1). Underscoring this imbalance in age and comorbidity, allogeneic transplant rates were 31% vs 16% for 7 + 3 and ven/HMA respectively (p<0.0005). More than 40% of initial 7 + 3 patients received second-line ven/HMA while less than 10% of ven/HMA patients received second line 7 + 3 or CPX-351. In unadjusted analysis, median OS (mOS) was 14 months for all patients and 22 months for 7 + 3 versus 10 months for ven/HMA (HR 0.52, 95% confidence interval CI 0.41-0.67, p-value <0.005, Fig 1). No subset had statistically significant higher OS with ven/HMA compared to 7 and 3; in multi-variate analysis controlling for all covariates with univariate p-value < 0.20 induction choice did not affect overall survival (limited to complete cases n=229, HR 0.72, p-value 0.21). Missing values in the HUP dataset were <5% for all baseline covariates; Flatiron dataset missing values ranged from 0-40% for covariates (e.g., sex and baseline LDH respectively). After balancing covariates and adjustment for missing values, survival remained superior in the 7+3 group (HR 0.71, p-value 0.026, 95% CI 0.53-0.94) (absolute standardized differences for all baseline variables were below 0.10). Regarding safety, early mortality was higher for ven/HMA (13% vs 6%, p=0.003). However, rates of febrile neutropenia and culture positive infection were higher for 7 + 3. Length of stay, including any admission prior to next cycle, was longer for 7 + 3 in the HUP cohort (among patients admitted for induction: average 25 days for ven/HMA vs 34 days for 7 and 3 p=0.0012; an additional 20% of ven/HMA patients were managed entirely outpatient). Conclusion In this large, multi-center real word study, of patients presumed to be eligible for either approach we found superior outcomes for 7 + 3. However, there was significant confounding by indication and imbalance between the groups. Adjusting for these differences, OS was still higher for 7 + 3 (p=0.026). In this real world dataset, the 7 + 3 cohort outperformed historical benchmarks (e.g., NCT02085408) in OS and early mortality, perhaps reflecting improved later lines of therapy and patient selection. Given the significant confounding by indication, uneven cross-over and greater lab-based AEs/longer length of stays for intensive chemotherapy, prospective studies (such as NCT04801797) must confirm superiority of intensive chemotherapy. Careful attention to factors predictive of response to non-7 + 3 based therapy may be as important as the characterization of side effects, quality of life and impact on allotransplant to select optimal therapies for all adult AML patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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

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 an investigational cultivated microbiome therapeutic rationally designed 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 to evaluate the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT that is currently enrolling at 4 sites. Study Design and 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 and stratified by conditioning regimen intensity. 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, subjects in both cohorts will receive 2 treatment courses (before and after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, and a conditional 3rd treatment course if the subject receives antibiotics (Table 1; Figure 1). Safety outcomes will be followed through 52 weeks post HCT. The primary endpoint is to evaluate 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 in placebo vs SER-155 arms. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. In April 2022, the SER-155 Data and Safety Monitoring Committee met as part of a planned review of available safety data from Cohort 1 and supported continuation of Cohort 1 enrollment. Summary: In this Phase 1b study, the feasibility, safety, and clinical efficacy of SER-155 is being assessed in the setting of allogeneic HCT. This trial will add to the expanding clinical experience of microbiome-directed interventions in allogeneic HCT recipients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Outcomes, Prognostic Factors and Therapeutic Management in Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type (ENKTL-NT) - Results of the Multicenter T-Cell Brazil Project

Introduction: Extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL-NT) is an aggressive, angiocentric, and extensively necrotic malignancy, universally associated with Epstein-Barr virus (EBV) infection. Although highly prevalent in South America, few studies involving cohorts from this region have been published. Brazil is the largest and most populous country in South America, but Brazilian data on ENKTL-NT are extremely scare. In order to fill this gap, the current study aims to describe clinical and laboratory characteristics, assess clinical outcomes, determine predictors of survival and compare responses between different therapeutic modalities applied in a multicenter cohort of Brazilian patients with ENKTL-NT. Methods: This is a retrospective, observational and multicenter study, involving 98 patients with ENKTL-NT diagnosed and treated at 20 different Brazilian institutions between January 2000 and December 2021. Endpoints included overall response rate (ORR), overall survival (OS) and progression-free survival (PFS). Survival curves were constructed using the Kaplan-Meier method and the Log-Rank test was used to assess the relationship between variables and outcomes. Univariate analysis was performed using the semi-parametric Cox test and multivariate analysis by Cox regression method or proportional ratios model. The results were presented in hazard ratio (HR) and 95% confidence interval (95% CI) and a p-value ≤ 0.05 was considered statistically significant. Results: The median age was 50 years (IqR 40-58) and 60.2% (59/98) were male. Sixty-three percent (62/98) had B-symptoms, 26.5% (26/98) had ECOG ≥ 2, 16.3% (16/98) had extranasal disease, 34.7% had advanced-stage III/IV, and 30.2% (29/98) had high-risk PINK score [Table 1A]. Table 1B summarizes the main therapeutic modalities, responses and associated adverse event profile among the 89/98 patients undergoing up-front treatment. With a median follow-up of 49.0 months (95% CI: 35.8-62.3), the estimated 2-year OS and PFS were 51.1% (95% CI: 40.4-61.6) and 17.7% (95% CI: 4.5-30.8), respectively. Among early-stage disease (IE/IIE) patients, the estimated 2-year OS were 81.3% (95% CI: 64.8-97.7) for SCRT (sequential chemoradiotherapy) followed by CHOP-like, 53.2% (95% CI: 29.3-77.1) for CCRT (concurrent chemoradiotherapy) followed by VIPD, and 50.5% (95% CI:21.4-79.5) for SCRT followed by asparaginase-based regimens, p=0.221 [Figure 1B]. CCRT-VIPD was associated with higher early-mortality (p=0.034), and higher rates of neutropenia (p=0.075), febrile neutropenia (p=0.043) and mucositis (p<0.001) [Table 1B]. Among advanced-stage (III/IV) disease, the estimated 2-year OS were 37.0% (95% CI: 8.9-65.0) for asparaginase-based regimens and 33.0% (95% CI: 1.9-68.5) for anthracycline-based regimens, p=0.851 [Figure 1C]. Chemoradiotherapy (CRT) was associated with benefit for OS (p=0.001) and PFS (p=0.007) compared to chemotherapy alone [Figure 1D and 1E]. In multivariate analysis, anemia (HR 2.052, p=0.038), lymphopenia [HR 3.600, p=0.012], advanced- stage disease (III/IV) [HR 3.101, p=0.007], bone marrow infiltration [HR 5.406, p=0.034] and omission of RT in up-front therapy [HR 2.791, p=0.023] were independent factors associated with decreased survival. Conclusion: High-dose EF-RT proved to be the cornerstone for the treatment of early-stage ENKTL-NT, and omission of this therapeutic modality was associated with decreased OS and PFS in Brazilian patients. In our real-life study, CCRT-VIPD regimen was poorly tolerated, and surprinsingly protocols based on anti-MDR agents were not associated with increased survival either in early- or advanced-stage disease. We also found that anemia, lymphopenia, advanced-stage (III/IV) and bone marrow involvement were independent predictors associated with poor clinical outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal