Myelosuppressive Chemotherapy Research Articles

Abstract PO1-07-05: Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device

Abstract Background Febrile neutropenia (FN) is a common complication that can arise in breast cancer patients receiving myelosuppressive chemotherapy and increases the risk of fatal infections. Despite better preventive strategies there are between 140,000 to 200,000 FN-related hospitalizations yearly. Quick detection and awareness of grade III neutropenia (Absolute Neutrophil Count [ANC] < 1,000/µL) or greater can be critical to managing FN and treatment scheduling and dosing in patients with breast cancer. The current gold standard for neutropenia detection is a peripheral blood collection that requires patients to come into the clinic. PointCheck™ is a novel, noninvasive technology that can monitor for grade III neutropenia or greater and enable prompt detection in the home by acquiring microscopy videos of superficial capillaries through the nailfold skin and analyzing those videos with computer vision AI algorithms. To evaluate the usability, diagnostic performance, and preliminary clinical utility of PointCheck™ on FN detection we conducted a multi-center observational usability and diagnostic study. Methods The present study included an overall cohort of 175 diverse cancer patients, with 70 breast cancer patients. The primary endpoint was to achieve a score over 80.8 on a standardized System Usability Scale (SUS). Secondary endpoint was achievement of diagnostic performance with an area under the curve (AUC) above 0.80. We also performed an exploratory analysis on the device's clinical utility. Eligible participants were introduced to the device, watched a tutorial video and were given a user manual. They used the device autonomously under the supervision of the clinical team. Usability data was collected using the SUS, the scoring system that has a scale between 0-100. PointCheck™ measurements were analyzed using AI algorithms and compared to same-day Complete Blood Counts (CBCs) collected within 90 minutes of the measurement to assess accuracy in classifying patients as grade III neutropenic or greater (< 1,000/µL), or non-grade III neutropenic (≥1,000/µL). In the exploratory clinical utility analysis, clinicians provided narrative insights by completing a Likert survey assessing how PointCheck™ would support or impact their clinical decisions. Results 81.4% of breast cancer patients scored above 80.8 on the SUS scale across all sites, with a mean SUS score of 87.7 (SD=13.2). Furthermore, the AI-based PointCheck™ classifier accurately discriminated neutropenia patients with an AUC = 0.90 in the overall cohort. In the exploratory analysis, a majority of clinicians (65.2%) agreed that the device could have helped better evaluate their patients (Table 1). Whereas almost 3 out of 4 clinicians (72.4%), described that the use of PointCheck™ could have avoided preparing a chemotherapy infusion if the patient was not ready due to grade III neutropenia or greater. Conclusions The present study showed that there is a high perception of usability of PointCheck™, indicating an above average user experience and falling within the top 10% of systems. Furthermore, we found that PointCheck™ can accurately detect grade III neutropenia or greater in a large cohort of patients including breast cancer patients. Application of PointCheck™ to clinical practice as a monitoring system can contribute to the early detection of FN and antineoplastic therapy management. Table 1: Clinical Utility Survey Results Citation Format: Juan Garcia-Mosquera, Manuel Alva, Toshiaki Iwase, Ganimete Lamaj, Pablo Tolosa, Rodrigo Sánchez-Bayona, José Pelaez-Escobar, Alberto Pablo-Trinidad, Ryan Benasutti, Aurélien Bourquard, Ian Butterworth, Alvaro Sánchez-Ferro, Carlos Castro-González, José Manuel Pérez-García, Alejandro Martínez-Bueno, Eva Ciruelos, Azadeh Nasrazadani. Preliminary Evaluation in Breast Cancer of PointCheck: a Noninvasive AI-Based Neutropenia Monitoring Device [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-05.

How Can Oncology Nurses and Advanced Practice Providers Reduce the Burden of Chemotherapy-Induced Febrile Neutropenia in the US?

Background: Neutropenia and febrile neutropenia (FN) are serious complications of myelosuppressive chemotherapy and present a considerable burden to patients with cancer. Febrile neutropenia is associated with increased risks of infection and hospitalization, a particular concern during the coronavirus disease 2019 (COVID-19) pandemic. Oncology nurses and advanced practice providers (APPs; including nurse practitioners, physician assistants, advanced practice nurses, and pharmacists) play a vital role in the management of patients with cancer and the prevention of infections. Objectives: The objectives of this article are to summarize the burden of chemotherapy-related neutropenia and FN in patients with cancer in the US and to evaluate the role of oncology nurses and APPs in preventing and managing FN. Methods: This article provides a narrative review of US studies reporting on the burden of FN, FN during COVID-19, adherence to guidelines for the use of prophylactic granulocyte colony-stimulating factors (G-CSFs), the involvement of oncology nurses in FN prevention, management, and patient quality of life, and inappropriate and/or incomplete G-CSF treatment. Findings: Despite advances in supportive care for patients with cancer receiving myelosuppressive chemotherapy, neutropenia and FN present a considerable burden to patients, particularly during the COVID-19 pandemic. Oncology nurses and APPs play a vital role in the appropriate and timely delivery of supportive care, which can improve patient outcomes and minimize treatment costs.

Mortality in patients with hematological malignancies, febrile neutropenia, and septic shock.

Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM and febrile neutropenia. We included all patients with hematological malignancies (HM) who presented fever and severe neutropenia, admitted to an oncological tertiary care center in Mexico City for one year. Two hundred ninety-two episodes of fever and severe neutropenia were documented; 68 patients (23.2%) developed SS. Documented clinical infection was different between SS and non-SS patients (94.1% vs. 63.4%, p < 0.001); pneumonia was the most frequent infection (36.8% vs. 23.2%, p = 0.02). Also, in SS vs. non-SS, there were more positive cultures (69.1% vs. 38.4%, p < 0.001), higher frequency of Gram-negative bacteria (89.3% vs. 63.9%, p < 0.001), particularly Escherichia coli (68% vs. 44.2%) and Klebsiella spp. (23.4% vs. 15.1%). There were no differences when multidrug-resistant (MDR) microorganisms were compared. In the multivariate analysis, associated risk factors for SS were: prolonged neutropenia, a documented site of infection, and having received highly myelosuppressive chemotherapy. Risk factors for mortality at 30 days were: older patients, prolonged neutropenia, and SS. Severe and prolonged neutropenia was associated with SS development and mortality at 30 days. ICU management should be offered to all critically ill patients with HM if long-term survival of the underlying malignancy is expected.

Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial

PurposeEvaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012–07-19).Methods232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle.ResultsEfbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7–8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0–2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug.ConclusionEfbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety.ClinicalTrials.gov identifierNCT01648322.

From in silico to in Vitro to In Vivo: Increasing Megakaryocytes to Treat Thrombocytopenia

Hematopoietic stem cells undergo a multi-step differentiation program through several precursor stages to give rise to megakaryocytes (Mk), which ultimately release platelets. Thrombocytopenia can manifest in various clinical settings and can adversely affect a patient's quality of life through easy bruising and risk of bleeding. An example is chemotherapy-induced thrombocytopenia (CIT) which occurs when myelosuppressive chemotherapy is given, especially with certain agents such as platinum analogs and cyclophosphamide. We used a single-cell RNA-sequencing approach to study the differentiation of hematopoietic stem cells to Mk progenitors (MkP) and delineated the trajectory that defines the transition of cells to the megakaryocytic lineage. Using our proprietary platform which pairs new approaches in computation and machine learning in drug discovery, we predicted small molecule interventions that could modulate the hematopoietic lineage direction to increase the differentiation towards MkP and subsequent increases in platelet counts. Using an in vitro 5-day CD34-based Mk differentiation assay we demonstrated that some of our predicted interventions increased generation of MkP from stem cells. Analysis of early MkP (CD34-CD235a-CD71+CD41b+CD42b-) and late MkP (CD34-CD235a-CD71-CD41b+CD42b+) by flow cytometry elucidated differential mechanisms of action such as induction of early or late MKP or both. We performed an 8-day study in healthy mice, which revealed that a selected set of compounds increased MkPs in vivo, consistent with our predicted cell behavior and in vitro findings. To evaluate a possible application for this MkP and platelet increases we tested the efficacy of one of our hit compounds CP3 in a CIT mouse model using Carboplatin. In this model, we recorded a &amp;gt;70 % reduction in platelet counts on day 9 post carboplatin administration, with platelet numbers recovering on day 13 and return to basal levels by day 21. To assess the efficacy of CP3, mice dosed first with this compound were challenged with carboplatin. The primary endpoint of this study was the ability of the compound to rescue mice from nadir of thrombocytopenia and accelerate recovery to baseline. Prior to carboplatin dosing, 7 days of CP3 dosing showed a dose dependent increase in platelet counts confirming our initial studies. However, CP3 dosing did not rescue platelet nadir or accelerate recovery to baseline in the CIT model. This study demonstrated the capacity of CP3 to increase platelets in a healthy BM environment but not under conditions of myelosuppression as seen in the CIT mouse model. Taken together, these findings highlight the benefits of our platform to predict compounds that modulate lineage differentiation towards MkP, and a resultant increase in platelet numbers in an animal model.

2089P Multi-cycle prophylaxis of long-acting granulocyte colony-stimulating factor in cancer patients at risk of febrile neutropenia due to myelosuppressive chemotherapy: A retrospective real-world study in China

2089P Multi-cycle prophylaxis of long-acting granulocyte colony-stimulating factor in cancer patients at risk of febrile neutropenia due to myelosuppressive chemotherapy: A retrospective real-world study in China

Using recombinant human G-CSF to treat chemotherapy-induced neutropenia over 3 decades: What is next?

Chemotherapy-Induced Neutropenia (CIN) is a potentially fatal side effect of cancer treatment, affecting &gt; 50% of cancer patients treated with chemotherapy. Clinical use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) has allowed for primary and secondary prophylaxis of CIN and its sequela (i.e., febrile neutropenia, fatal infection) during myelosuppressive chemotherapy. Here, we review the translation and properties of first, second, and third-generation rhG-CSF molecules, including filgrastim (Neupogen, FDA approved in 1991) and biosimilars, pegfilgrastim (Neulasta, FDA approved in 2002) and biosimilars, and F-627 (Ryzneuta, NMPA approved in 2023), a novel long-acting rhG-CSF agent developed this past decade. Even with the development of increasingly personalized and targeted cancer therapy, chemotherapy, and stem cell transplantation remains a backbone for the majority of patients with advanced cancers, especially in the hematopoietic system. As such, more than 20 million cancer patients have been treated with rhG-CSF drugs since the first approval of filgrastim. In the next decade, we envision third-generation rhG-CSF products such as Ryzneuta lowering costs to patients and healthcare providers, expanding access to this essential medication for cancer patients worldwide, particularly for patients who require more aggressive chemotherapy treatment.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy

PurposeNeutropenia, defined as a number of neutrophils in patients’ blood specimen lower than 1500 cells/μm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60–89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN.MethodsThe study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration.ResultsSixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45–27.29; p < 0.01).ConclusionsOur observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

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.

Efficacy and safety of PEG-rhG-CSF versus rhG-CSF in preventing granulocytopenia in sarcoma patients receiving doxorubicin combined with ifosfamide: A prospective, randomized, non-inferiority phase II study.

e24173 Background: Prophylactic use of rhG-CSF is routinely recommended in patients with a high risk of febrile neutropenia (FN) after chemotherapy. Currently, rhG-CSF is mostly used in clinical practice. However, PEG-rhG-CSF tends to be a substitute due to its convenience and long-acting effect. Regarding concerns about its efficacy and safety, whether PEG-rhG-CSF could be prophylactically used after these regimens with a high risk of FN is still in doubt. Doxorubicin combined with ifosfamide is commonly applied in sarcoma patients and is one of the most serious myelosuppressive chemotherapy regimens in solid tumors. We compared the efficacy and safety of PEG-rhG-CSF with rhG-CSF in the prevention of severe granulocytopenia and FN, in patients receiving this representative regimen. Methods: This was a single-center, prospective, randomized, crossover, non-inferiority phase II trial. Patients with sarcoma suitable for doxorubicin combined with ifosfamide treatment were enrolled. All patients received 2 cycles of chemotherapy and were randomly assigned to either the AOB group (PEG-rhG-CSF used in 1st cycle and rhG-CSF in 2nd cycle) or BOA group (rhG-CSF used in 1st cycle and PEG-rhG-CSF in 2nd cycle). Blood monitoring every other day until ANC ≥ 2×109/L in two consecutive tests. The primary endpoints were the frequency and duration of grade 4 granulocytopenia after prophylactic use of PEG-rhG-CSF and rhG-CSF respectively, the secondary endpoints were the frequency and duration of febrile neutropenia, and proportion of antibiotic use. Results: From Jan 1, 2018 to Aug 31, 2021, 70 patients were enrolled, 35 each in AOB and BOA. There were no statistical differences in the incidence and duration of grade 4 granulocytopenia (85.7% vs. 77.0%, p = 0.1; 1.34d vs. 1.41d, p = 0.70), the proportion and duration of febrile neutropenia (12.8% vs. 8.2%, p = 0.77; 0.6d vs. 0.8d, p = 0.74), and the proportion of antibiotics used (19.1% vs. 14.9%, p = 0.79) when comparing PEG-rhG-CSF vs. rhG-CSF in prophylactical use. The incidence of grade 4 granulocytopenia in both groups was comparable in 1st cycle (90.9% vs. 96.0%, p = 0.47), but in 2nd cycle it was significantly lower in AOB than that in BOA (54.5% vs. 88.0%, p = 0.01). The lowest value of ANC was higher in AOB in 2nd cycle (0.32G/L vs. 0.12G/L, p = 0.03). Conclusions: This study demonstrated PEG-rhG-CSF could prevent granulocytopenia and FN in sarcoma patients receiving doxorubicin combined with ifosfamide, with comparable efficacy and toxicities as rhG-CSF. Considering the convenience in use and patient compliance, PEG-rhG-CSF could be an effective and reasonable alternative to rhG-CSF. Clinical trial information: ChiCTR1900021945 .

Eflapegrastim (Rolvedon) for prevention of chemotherapy-induced febrile neutropenia.

Eflapegrastim-xnst (Rolvedon [Spectrum]; previously called Rolontis), a granulocyte colony-stimulating factor (G-CSF) conjugated to an Fc fragment of human IgG4, has been approved by the FDA to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive chemotherapy that can cause clinically significant febrile neutropenia.

Health professionals’ preferences with the use of pegfilgrastim on-body injector at oncology centers in 8 cities in Colombia

BackgroundFebrile neutropenia associated with some chemotherapy regimens can lead to potentially fatal complications and high health care costs. Administration of pegfilgrastim using an On-Body Injector (OBI) may be more convenient for cancer patients and physicians in countries with limited access to high-complexity healthcare. This study aims to describe physician and nurse preferences regarding different options for administration of pegfilgrastim at cancer centers, the chemotherapy schemes for which pegfilgrastim is most frequently prescribed and how healthcare providers prioritize certain administration schemes according to patients’ access to healthcare services.MethodsObservational, descriptive, cross-sectional study and survey, conducted between 2019 and 2020, to describe physician and nurse preferences regarding options for administration of pegfilgrastim at cancer centers, the demographics of the study population and characteristics of participating cancer centers. It included 60 healthcare professionals practicing at oncology centers from 8 cities in Colombia who were contacted and surveyed via telephone. Quantitative continuous variables were summarized using central tendency and dispersion measures.ResultsIt was found that 35% of participants are haemato-oncologists, oncologists or hematologists, 30% are general practitioners, and 35% are other healthcare professionals (i.e., nurse, oncology nurse and head nurse). Our study shows that 48% of physicians prefer the use of OBI, particularly in the scheme of 24 h after myelosuppressive chemotherapy administrations. Regardless of patient frailty and travel time to the clinic, over 90% of healthcare providers (HCPs) prefer to prioritize preventing the patient from having to return to the clinic for pegfilgrastim administration as well as to increase healthcare staff availability through the use of OBI.ConclusionsThe present study is the first one in Colombia that sought the reasons behind HCPs’ choice to use OBI pegfilgrastim. Our results indicate that most professionals prefer to avoid the patient having to re-enter the care center for pegfilgrastim administration to facilitate access to healthcare for patients; patient characteristics and ease of transport are determining factors for respondents when choosing an option for drug administration. We found OBI is the preferred alternative by most HCPs and a good resource optimization strategy in the context of cancer patients’ health care in Colombia.

Pre-Chemotherapy Dental Screening: Is There Additional Diagnostic Value for a Panoramic Radiograph?

The oral cavity is a potential source of infectious complications in patients treated with myelosuppressive chemotherapy (CT). Pre-chemotherapy oral examination to identify foci of infection is recommended, but it is unclear whether this should include panoramic radiography. The present study aimed to evaluate the additional diagnostic merit of panoramic radiography as part of pre-CT oral screening. Patients with solid tumors scheduled to receive a myelosuppressive CT were eligible. The foci definition followed the guidelines of the Dutch Association of Maxillofacial Surgery. Oral foci assessed by clinical evaluation and panoramic radiography were compared. In 33 out of 93 patients (35.5%), one or more foci were identified by clinical examination, whereas in 49.5% of patients, panoramic radiography showed pathology. In 19 patients, an oral focus was missed by clinical examination only, whereas in 11 patients, panoramic radiography indicated periodontal bone loss, but advanced periodontitis was not substantiated by clinical examination. Panoramic radiographs complement clinical examinations and have additional diagnostic value. Nevertheless, the additional merit seems small, and the clinical relevance may vary depending on the anticipated risk of developing oral complications and the need for detailed diagnosis and rigorous elimination of oral foci prior to the start of cancer therapy.

Breakthrough invasive fungal infection in patients with myeloid malignancy receiving posaconazole tablet prophylaxis: clinical features, risk factors, and posaconazole profiles.

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for breakthrough IFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady-state and breakthrough IFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. Ten patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P<0.001). History of allogeneic hematopoietic stem cell transplantation (OR 6.27; 95% CI 1.63-24.09), prolonged neutropenia≥28 days (OR 4.33; 95% CI 1.20-15.70), and low plasma PSC concentration<0.7μg/mL (OR 16.33; 95% CI 4.15-64.26) were risk factors for bIFI. The optimal cut-off value of plasma PSC concentration predicting bIFI was 0.765μg/mL (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablets prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.

Grade 4 Neutropenia Frequency as a Binary Risk Predictor for Adverse Clinical Consequences of Chemotherapy‑Induced Neutropenia: A Meta-analysis

Neutropenia is the major toxicity of myelosuppressive cancer chemotherapy. Grade 4 neutropenia (Gr4N) is a measure of chemotherapy-induced neutropenia (CIN) severity. We conducted a meta-analysis of CIN data. Gr4N incidence was significantly correlated with febrile neutropenia (FN), days of severe neutropenia (DSN), and nadir absolute neutrophil count (ANC), which are all important predictors of morbidity. With a Gr4N threshold of 65%, both FN and DSN were below levels for low risk of adverse CIN outcomes. Gr4N was highly predictive for adverse CIN outcomes, and a 65% threshold demarcated low vs. high risk for FN and other adverse CIN outcomes.

Higher incidence of pegfilgrastim-induced bone pain in younger patients receiving myelosuppressive chemotherapy: a real-world experience

BackgroundPegfilgrastim is widely used for the prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy for various types of cancer. However, pegfilgrastim-induced bone pain (PIBP) is a relevant adverse event occurring during cancer treatment. Thus, we aimed to determine the risk factors for PIBP in real-world clinical practice.Main bodyWe retrospectively collected the clinical records of patients who received pegfilgrastim to support myelosuppressive chemotherapy with at least a 10% risk of FN between 2015 and 2018 at our center. Patients received pegfilgrastim 3.6 mg between days 2 and 7 after chemotherapy administration (day 1) for primary or secondary prophylaxis against FN. All adverse events were recorded according to the Common Terminology Criteria for Adverse Events. Patients who experienced intermittent bone pain in the back, femur, or other anatomic sites after the pegfilgrastim administration were considered to have PIBP. To evaluate the relationship between PIBP incidence and patient characteristics, we performed univariate and multivariate logistic regression analyses to calculate the odds ratios (ORs) of possible risk factors for PIBP. We analyzed the data of 305 patients (median age: 63 years), who underwent 1220 chemotherapy cycles with pegfilgrastim per cycle. Univariate analysis revealed that female sex (vs. male sex), younger age (< 55 years vs. ≥ 55 years), and solid cancers (vs. hematologic cancers) had significantly higher ORs (p < 0.05). However, only younger age (< 55 years) was an independent risk factor for PIBP on multivariate analysis (OR 3.62, 95% confidence interval 1.51–8.69, p = 0.004).ConclusionsYounger age (< 55 years) was significantly associated with a higher risk of PIBP among patients receiving chemotherapy with a ≥ 10% risk of FN. Therefore, oncologists should meticulously formulate management plan for PIBP in younger patients after administering pegfilgrastim.

Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review

BackgroundFebrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim’s value for money remains unclear.ObjectiveTo systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.MethodsA systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020.ResultsWe identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17–97.4%) and mortality rates (5.8–8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit.ConclusionsMost studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

Real-World Use of Granulocyte-Colony Stimulating Factor in Patients with Breast Cancer from Alberta, Canada.

There are limited published data in the Canadian healthcare system on the use of granulocyte colony-stimulating factor (G-CSF) among patients with breast cancer. This study characterized real-world G-CSF use during the period surrounding the introduction of filgrastim biosimilar. Electronic medical records were reviewed retrospectively for patients with breast cancer who received moderately or highly myelosuppressive (neo)adjuvant chemotherapy from 2008 to 2019 in Alberta, Canada. Trends in G-CSF usage were plotted to elucidate temporal variations and multivariable regression models were constructed to identify clinical factors associated with G-CSF use. We included 6662 patients in our analyses. G-CSF was used in 57.1% of patients during their treatment trajectory. Among the 3801 patients who were treated with G-CSF, the majority received pegfilgrastim only (91.5%; n = 3477) versus filgrastim only (5.7%; n = 217). G-CSF use increased linearly more than two-fold over the 11-year study period. Predictors of G-CSF use included younger age, south zone of residence, higher neighborhood education, inferior disease stage, highly neutropenic risk chemotherapy, and more recent chemotherapy initiation. Despite increasing G-CSF usage over time, an appreciable proportion of patients for whom G-CSF prophylaxis is recommended did not receive it. G-CSF use could be further optimized to align with supportive care clinical guidelines and reduce the impact of neutropenia and its associated complications.

A Bioinformatic Approach to the Clinical Evaluation of Linear Commitment Versus Cloud (Continuum of Low Primed UnDifferentiated) Models for Hematopoiesis Using Plinabulin Clinical Trial Data

Introduction An alternative to the classical Lineage Commitment model for hematopoiesis is the Continuum of Low Primed UnDifferentiated (CLOUD) model (Velten, Nat Cell Biol 2017). Lineage Commitment and CLOUD data are largely derived from in-vitro methods. In-vivo clinical data that is devoid of analytical method-induced 'bias' is sparse. Plinabulin (Plin), is a novel agent that prevented chemotherapy-induced-neutropenia (CIN) in cancer patients (pts) through protection of bone marrow stem cells (Tonra, 2020; Blayney, ASH 2021). Plin, therefore could serve as a pharmacological interventional approach to evaluate Linear Commitment versus CLOUD for hematopoiesis in an in-vivo, human setting. Peripheral blood cell counts (PBCs) from the myeloid, lymphoid, and erythroid lineages in cancer pts receiving myelosuppressive chemotherapy (Chemo) with and without Plin were analyzed using bioinformatics. Method PBCs from cancer pts (Breast, NSCLC, HRPC) receiving Chemo (TAC [docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2; Study 106; NCT03294577] or docetaxel 75 mg/m2 alone; Study 105 NCT03102606), with Plin doses of 5, 10, 20, 30 mg/m2 (or equivalent) or placebo (Plac; without plinabulin) were collected at screening, predose (cycle (C) 1 day (D) 1,) and at 24 hours after Chemo with or without Plin (C1D2). Plin was given as a single dose by 30 min IV infusion, 30 mins after (the last) Chemo on D1. All pts (with and without Plin) had received dexamethasone 16 mg per day on D-1, 1, and 2 as premedication for docetaxel (and TAC). Blood draws for absolute counts of PBCs, segmented neutrophil (N), band neutrophil (BAND), monocyte (M), eosinophil (E), basophil (B), lymphocyte (L), erythrocyte (RBC), platelet (P), and immature cells, were analysed by Central Laboratory (Covance). Bioinformatic analysis was performed by FIOS Genomics. To detect treatment-specific effects, exploratory principal component analysis (PCA) and Pearson correlation analysis were performed. 'Limma' linear modelling was used to assess treatment impact on cell counts (C1D1 vs screening; C1D2 vs C1D1) and changes in cell counts (screening to C1D1; C1D1 to C1D2), adjusting for relevant clinical variables. Further correlation and clustering analyses per hematopoietic hierarchy (MEP, GMP, and GLP) were performed to determine correlations between change in cell abundance on C1D2 vs C1D1 for Plin and Plac. Significant differences were defined as those with a P-value adjusted for multiple testing of P < 0.05. Result Following Plac, cell types from myeloid, lymphoid, and erythroid lineage demonstrated significantly decreased abundance on C1D2 vs C1D1, reflecting myelosuppression by Chemo. In contrast, following Plin, an increase in abundance for all GMP-derived myeloid cells (N, M, B, and E) were observed, and in Plin dose-dependent manner. In absolute counts, GMP-derived myeloid cells had increased significantly with Plin at C1D2 vs C1D1, suggesting not only protection, but also stimulation of GMP cells by Plin. Furthermore, significant increases on C1D2 vs C1D1 in immature post-GMP progenitor cells (BAND, metamyelocytes, and myelocytes), were observed with Plin, but not with Plac, further suggesting GMP stimulation by Plin. For CLP and MEP-derived cells, decreases were seen with Plin, however, to a much smaller extent compared to Plac, suggesting some degree of protection with Plin. Cell cluster analysis showed inter-correlation in abundance of GMP-derived cell types (N, M, B, and E), which is in support Lineage Commitment. Relative abundance in cells derived from the CLP and MEP were also intercorrelated with abundance of GMP-derived cells, further supporting Lineage Commitment. Conclusion Using bioinformatic analyses, we demonstrated that Plin not only exerts protective, but also stimulatory effects on GMP cells under myelosuppressive conditions. The abundance of immature PBCs derived from the GMPs is in further support of stimulation of GMP cells with Plin. The data also suggests a degree of protective effect with Plin on CLP- and MEP-cells. The interdependence in abundance of mature PBCs derived from GMP cells, but also from CLP- and MEP-derived cells, is strongly supportive of Lineage Commitment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal