Anemia Grade Research Articles

Exploring the role of bispecific and CAR-T cell therapies in gastric cancer: A systematic review and meta-analysis.

465 Background: Gastric cancer (GC) is associated with significant mortality due to the limited efficacy of current conventional treatments, necessitating the need for novel therapies. In this systematic review and meta-analysis, we aim to explore the potential role and outcomes of bi-specific antibodies and chimeric antigen receptor T-cell (CAR-T) immunotherapy in treating GC. Methods: Using PRISMA guidelines, searches were conducted on PubMed, Cochrane, and Clinicaltrial.gov for 'Gastric cancers', 'bispecific antibodies', and 'CAR-T therapy' as of March 30, 2024. Out of 35 studies, 9 were selected for pooled analysis in R (v4.3.3) using the Der Simonian-Laird Estimator, calculating inter-study variance and extracting data with 95% CI. Results: 138 gastric cancer (GC) patients from 2 phase I (22.22%), 3 phase Ib (33.33%), 3 phase II (33.33%), and 1 case report (11.11%). Median age was 57 (28-77) years, and 76% (31/41) were male. Bispecific antibodies were MCLA-128 (25/138), catumaxomab (15/138), AK104 PD-1/CTLA-4 (16/138), ABL 001 DLL4VEGFA (19/138), and KN026 (25/138) while CART therapy was CT041 (38/138). The pooled overall response (OR), partial response (PR), and complete response (CR) for bispecific antibodies was 37% (95% CI, 0.12-0.71, I2=76%, n=100, p <0.01), 21% (95% CI,0.05-0.55, I2=73%, n=85, p<0.01), and 11%(95% CI, 0.02-0.38, I2=63%, n=85, p=0.03) respectively, while the pooled OR, PR, and CR for CART was 56% (95% CI, 0.40-0.71, I2=0%, n=38, p=0.41), 53%(95% CI, 0.36-0.69, I2=0%, n=38, p=0.38, ), and 12% (95% CI, 0.02-0.42, I2=38%, n=38 p=0.2), respectively. The pooled disease control rate was 75% (95%CI,0.46-0.92, I2=79%, n=80, p < 0.01) for bispecific antibodies and 27% (95% CI,0.16-0.40, I2=0%, n=65, p=0.37) had the stable disease while pooled incidence of progressive disease was 18% (95% CI,0.09-0.31, I2=0%, n=55, p=0.53). The median progressive free survival was 6.74 months, with a median overall survival of 14.75 months. Common adverse effects included anemia, diarrhea, fatigue, and cytokine release syndrome grades 1 or 2. Conclusions: This analysis shows promising results in GC patients using bi-specific antibodies and CAR-T cell therapy. However, further clinical trials are needed to fully explore their potential.

Haematological toxicity of PARP inhibitors in advanced ovarian cancer: A systematic review and meta-analysis.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed, EMBASE and Cochrane databases, and international meeting abstracts were searched systematically for clinical trials concerning the use of PARPis in patients with OC. The search deadline was 30 March 2024. The pooled incidence of all grades and grade 3or more (≥G3) anaemia, neutropenia and thrombocytopenia were analysed. Subsequently, risk ratios (RRs) were calculated for all grades and ≥G3 AEs of PARPis compared with non-PARPis from randomized controlled trials. In total, 12 phase II/III trials with olaparib, niraparib and rucaparib were included in this study. Anaemia was the most common all grade (28.8%) and ≥G3 (12.1%) AE. The administration of PARPis increased the risk of developing all grade anaemia [risk ratio (RR)=2.44], neutropenia (RR=3.15) and thrombocytopenia (RR=4.66) significantly compared with non-PARPis. Similarly, a significant increase in the risk of ≥G3 anaemia (RR=5.73) and thrombocytopenia (RR=5.44), and a non-significant increase in the risk of neutropenia (RR=3.41) were detected. In patients with advanced OC, PARPis increase the risk of haematological toxicity compared with other treatments (high-quality evidence). Clinicians should be aware of this risk and the correct management, as these drugs are highly employed in these patients.

Durable and Drastic Response to the Trastuzumab, Letrozole, Abemaciclib, and Goserelin Combination as First-Line Therapy in HER2-Positive and Hormone Receptor-Positive Metastatic Breast Cancer: A Case Report

Introduction: Chemotherapy combined with anti-human epidermal growth factor receptor 2 (HER2)-targeted therapy is currently a standard treatment for advanced HER2/HR-positive breast cancer (BC), although evidences showed that HR expression compromised effectiveness of the treatment. While cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapy is a key therapy for the BC with HR expression, data on the effectiveness and safety of CDK 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic BC are limited. Case Presentation: Here, we report a case of a 46-year-old premenopausal woman diagnosed with stage 4 HER2/HR-positive invasive ductal carcinoma from both right and left breast with hypermetabolic activities in multiple lymph nodes, adrenal, bone, and skin. Interventions: Due to the patient’s refusal to use chemotherapy, she was started on goserelin, abemaciclib, letrozole, and trastuzumab. Outcomes: The patient’s symptoms were relieved with near resolution of the primary breast mass and nearly all of the metastatic sites. Metabolic resolution was observed in bone lesions. The disease was under control for 57 weeks. During the treatment, neutropenia (grade 1–2) and anemia (grade 1) occurred, which spontaneously recovered. Additionally, diarrhea improved after symptomatic treatment. Conclusion: We believe that the combination of trastuzumab, hormone suppression, and abemaciclib is a practicable and effective treatment for HER2-positive and HR-positive metastatic BC in premenopausal patients who cannot tolerate the first-line chemotherapy.

Influence of dosimetry accuracy on the correlation with treatment outcome in a preliminary PSMA radiopharmaceutical therapy study.

Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice. In this retrospective study, we analyzed data from 21 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) who underwent multiple cycles of 177Lu-PSMA-617 RPT treatment. Cumulative dosimetry of all the treatment cycles was calculated using both the standard multi-time point dosimetry (MTPD) method and the single time-point dosimetry (STPD,Hänscheidapproximation) method for the same cohort. Their correlations with treatment outcome (PSA decline rate and overall survival, OS) and complication risk (anaemia grade) were investigated. The Fisher's Z-Transformed test was performed to statistically evaluate the difference between the correlations. STPD showed a non-significant difference in correlation with PSA decline rate, despite a mean percentage error (MPE) of up to 36.44% in tumor dosimetry compared to MTPD (MTPD: rho = -0.39, p < 0.001; STPD: rho = -0.46, p < 0.001; Z = 0.58, p = 0.56). Both STPDtotal and MTPDtotal demonstrated a significant impact on OS (STPDtotal: Hazard Ratio = 1.05, p < 0.05, log-transformed MTPDtotal: Hazard Ratio = 3.41, p < 0.05, log-transformed STPDtotal: Hazard Ratio = 8.06, p < 0.05). Additionally, despite a MPE of up to -40.26% in bone marrow dosimetry, STPD showed a non-significant difference in correlation with anemia grade (MTPD: rho = 0.35, p < 0.001; STPD: rho = 0.40, p < 0.001; Z = -0.39, p = 0.70). The preliminary findings from a small cohort indicate that the reduced accuracy of a clinically simplified protocol may not diminish the clinical therapy outcome predictive value of dosimetry. Future thorough systematic investigations may be needed to determine the clinically acceptable level of accuracy for dosimetry.

Prevalence and demographic distribution of anaemia among those visiting a teaching hospital located in tribal predominant block of Jharkhand: Retrospective record based analysis.

Anaemia is a major public health concern in developing countries, with cases increasing rapidly among women, young girls, and children under age 5. This study aimed to estimate the prevalence of anaemia and to identify the age and gender distribution of anaemia among those attending IPD/OPD of a teaching hospital located in the tribal block. The study was conducted at a multispecialty tertiary care hospital in tribal predominant area, Jharkhand, India. A retrospective, chart-based study design was adopted to achieve the objectives. All inpatient case records available from the Department of Laboratory Medicine and the electronic hospital information system of the institute were reviewed between January 1, 2021, and January 31, 2024. A total of 15004 reports were screened for detecting anaemia, of them 7095 (47.3%) were males and 7909 (52.7%) were females. The overall prevalence of any grade of anaemia was found in 6579 (43.8%; 95% CI: 43.1-44.6). Univariate logistic regression analysis to predict status of anaemia among study participants showed the odds of being anaemic was 1.5 times (95% CI: 1.2-2.1) higher among those with age >60 years compared to those who were in the age group of 1-4 years. Females had 2.3 times (95% CI: 2.2-2.5) higher odds of having anaemia than males. This study shows that half of the patients attending hospital are anaemic and the burden increases as the age increases and highest among elderly >60 years. The results of our secondary data analysis should contribute to better screening and identifying the cases among people attending the hospital and also could aid planning services at the primary care level.

Comparison of CAR T-cell and bispecific antibody as third-line or later-line treatments for multiple myeloma: a meta-analysis

BackgroundCAR-T-cell therapy and bispecific antibody have revolutionized the treatment landscape for multiple myeloma. However, there is currently a lack of studies comparing the efficacy and safety of these two approaches....

Initial Experience with [177Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction.

[177Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [177Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [177Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [177Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer-associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0-6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3-16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer-associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [177Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence-based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

Bone marrow toxicity in patients with locally advanced cervical cancer undergoing multimodal treatment with VMAT/IMRT: are there dosimetric predictors for toxicity?

PurposeFor women with locoregionally advanced cervical cancer, the standard of care treatment is the curatively intended chemoradiation therapy (CRT). A relationship between bone marrow (BM) dose–volume histograms (DVHs) and acute hematological toxicity (HT) has been debated recently. Aim of this study was the evaluation of BM dose constraints and HT in a contemporary patient cohort.MethodsRadiation treatment plans of 31 patients with cervical cancer (FIGO stage IIB–IVB) treated with intensity-modulated radiotherapy and simultaneous chemotherapy were explored retrospective. Pelvic bones (PB) and femoral heads (FH) were contoured and DVHs were correlated with white blood cells (WBC), hemoglobin levels and platelets.ResultsComparing the absolute blood levels with the dose volumes of both FH and PB the data showed a significant correlation between WBC and the median dose of the FH and the median dose, V30Gy, V40Gy and V50Gy of the PB. A correlation between the toxicity grade of anemia and mean dose, maximum dose and V5Gy of the PB was found. Counting the highest grade of HT of all three blood levels of each patient, significant correlations were found for the mean and median dose, V30Gy, V40Gy and V50Gy of the PB.ConclusionThe results show that blood levels may correlate with distinct dosimetric subvolumes of critical bone marrow compartments with a potential impact on therapeutic outcome and treatment-related toxicity. The data presented are in line with the previous findings on the relevance of dosimetric exposure of pelvic bony subvolumes.

Study on incidence and clinical profile of anemia in children aged 1 years to 15 years attending tertiary care hospital

Background: Children are considered as an important asset for any country and their health as one of the important indicators of a healthy country. There are various factors influencing children's health, with anemia being one of them. Anemia is a major global health problem, especially in developing countries like India, despite the fact that this problem is largely preventable and easily treatable. Methods: It is a descriptive study conducted in 140 children aged 1 year to 15 years who presented with anemia in the department of pediatrics at Navodaya Medical College Hospital and Research Center, Raichur. Aim was to study the incidence and profile of anemia in children aged 1 years to 15 years. Results: A total 0f 140 cases aged between 1- 15 years were included in the study. The highest number of cases occurred in the 11-15 years age group (38.5%), followed by the 6-10 years group (35.0%). There is more female preponderance in this study (55.7%) compared to males (44.2%). Moderate degree of anemia was the commonest grade of anemia (42.8%) The most common cause of anemia in this study was iron deficiency, accounting for 58 cases (41.4%) followed by 17 cases (12.1%) had megaloblastic anemia. Conclusions: Iron deficiency anemia is a preventable cause of cognitive impairment, and early interventions can prevent the morbidity and mortality associated with anemia. Despite the implementation of national programs to combat iron deficiency, the problem persists. Early detection of anemia among these children enables the planning of suitable interventions, such as nutritional education for mothers, growth monitoring, nutritional supplementation, deworming, and more, to effectively address and mitigate the issue.

Patterns of Geriatric Anemia – A Clinicopathological Study

Background : Anemia is a common condition in elderly especially in hospitalized geriatric patients and is known to be associated with increased morbidity and mortality. The UN agreed cut off to refer to the older population is 60years and above. Anemia in the elderly is defined as a haemoglobin concentration below12 gm/dl in women and below 13gm/dl in men. Objectives: To study the grade and patterns of anemia in Geriatric age group of both sex with clinicopathological correlation. Materials and Methods: It is a Prospective study of 2 years from May 2018 to April 2020 carried out in KIMS, Hubbali. A statistically significant sample size was 400. Results: Among the total geriatric cases of 400, males were 233 (58.25%) and females were 167 (41.75%). In which majority of them were in the age group between 60-69 years that is 237 (59.25%) cases, followed by 121 (30.25%) cases, 38 (9.5%) cases and 4 (1%) cases were in the age group between 70-79 years, 80-89 and above 90 years respectively. The study showed that majority of the cases belonged to the Grade 1 anemia (69.25%). On smear examination most common morphological pattern was Normocytic Normochromic Anemia (75%), followed by Microcytic Hypochromic Anemia (18%). On clinical history correlation, majority of them were asymptomatic 52% and 38% of cases presented with fatigue. Conclusion: The study concludes that diagnosing different morphological patterns of geriatric anemia and its clinical correlation helps in reducing the morbidity and mortality of geriatrics related to anemia and also facilitate the clinicians to improve the treatment protocols and prophylactic therapy. Keywords Geriatrics, Patterns, Anemia

Bioanalytical method validation for therapeutic drug monitoring of olaparib in patients with ovarian cancer

Olaparib, an oral poly-ADP ribose polymerase (PARP) inhibitor, is a relatively new anticancer drug. It is essential to find TDM-guided dosage for better safety and tolerability of patients. However, first, it is important to develop a suitable analytical method to conduct reliable TDM. The aim of the study was the validation of UPLC-MS/MS method for TDM of olaparib in patients with ovarian cancer, with a particular attention to optimization of recovery. The validation of the method under analysis were accomplished by the ICH guidelines. The recovery of olaparib was optimized with the Central Composite Design (CCD). The TDM study was conducted on 10 patients with ovarian cancer treated with olaparib. The method validation was characterized by good precision (CV &lt;9.09%), accuracy (89.23-111.08%) and linearity (r=0.9993) within the range of 100-20,000 ng/mL, with limits of detection of 30 ng/mL. The ten-minute shaking time combined with 100% acetonitrile resulted in an estimated value of 98% for recovery and the observed value of 98%. The olaparib concentrations in the patients’ plasma were 1078.2-16773.8 ng/mL. A wide range of olaparib concentrations was observed in the patients reported adverse reactions included: anemia (grade 1, n=2), neutropenia (grade 1, n=1), and hyperkeratinemia (grade 1, n=1). The method validation included all required procedures showing that the measurement of olaparib concentrations in the plasma was reliable for the intended application, such as TDM.

Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: A single-centre retrospective study.

e13135 Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Methods: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n=45) and platinum-based therapy (n=51). The follow-up period for all patients ended on December 31st, 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median PFS compared to platinum-based (hazard ratio (HR)=0.41, p=0.006), nab-paclitaxel-based (HR=0.36, p=0.001) and other chemotherapy (HR=0.39, p&lt;0.001). Also, eribulin induced a remarkable prolongation of the median OS duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusions: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted. Clinical trial information: NCT05953909 .

Clinical Implications of Anemia Among Eastern Sudanese HIV Survivors.

Background In HIV patients, anemia is the most common hematopoietic consequence, and it has a major influence on life satisfaction, morbidity, and survival. The epidemiology of anemia in this cohort in Sudan, however, is poorly characterized. Aim This study aims to assess the prevalence of anemia and its implications among HIV-positive patients. Methods An observational case-control study was administered in 44 clinical HIV-positive cases at the Sudan National AIDS Program (SNAP), Red Sea State, Sudan, between January 2018 and December 2019. A total of 44 HIV-negative subjects as controls were enrolled. HIV-infected patients' demographic and clinical data, involving anemia and its outcome, were examined. WHO threshold was used to rank the clinical course of anemia in these patients. Results Of the 44 HIV patients examined, the mean age was 33.0 ± 11.2 years. Thirty (68.1%) were males, and 14 (29.8%) were females. The overall prevalence of anemia was 63.6% (95% CI 57.8-69.94%): mild grades of anemia at 25% (95% CI 14.4-34.4%), moderate grades of anemia at 36.4% (95% CI 28.7-43.2%), and severe anemia at 2.3% (95% CI 1.3-3.3%). In this study, 18 (64.3%) anemic patients showed normocytic thin smear pictures, among whom 44.3% were males and 20.5% were females. Microcytic anemia was seen in 17.8% of patients, while autoimmune hemolytic anemia was also detected in 17.8% of patients. The prevalence of anemia increased significantly with decreasing total lymphocyte count (TLC): 6.8% and 13.6% among patients with TLCs <1,000 and 1,000-4,800 cells/mm3, respectively (P = 0.016). Male sex was significantly associated with increased odds of anemia (OR 1.90, P = 0.049). Conclusion Anemia is a public comorbidity among HIV patients in the east of Sudan. Normocytosis is the most prominent form of anemia related to hypoproliferation in eastern Sudan, an event that can be triggered either by HIV chronicity or its combination with nutritional inadequacies. To prevent anemia progression and promote quality lifestyles, timely screening and appropriate therapy for anemia are critical, particularly for those with a low TLC.

Validation of new invasive digital hemoglobinometer for hemoglobin estimation as point-of-care device among pregnant women in a facility setting India

Background: Anemia poses a significant health challenge for pregnant women (PW), and accurate and timely diagnosis is essential for effective management. Objective: The objective was to assess the diagnostic validity of the new digital hemoglobinometer for hemoglobin against laboratory-based hematology autoanalyzer among PW. Methodology: The study was conducted at a secondary-level healthcare facility among 204 pregnant women to be sampled conveniently, their sociodemographic and iron intake data collected, and hemoglobin levels assessed using a digital hemoglobinometer (Device A) and a hematology analyzer. Specificity, sensitivity, PPV, NPV, diagnostic accuracy, and method agreement were evaluated via Bland-Altman analysis and Lin's concordance correlation coefficient. Results: The proportion of anemia using the Device A was 64.7% while the hematology analyzer reported a proportion of 52.9%. Device A showed a sensitivity of 97.22%, specificity of 80.30%, and diagnostic accuracy of 86.3%, with substantial agreement indicated by Cohen's kappa coefficient (kappa = 0.72) and the weighted kappa coefficient for different grades of anemia was 0.67. Bland-Altman analysis revealed a mean difference (bias) of -0.28 (± 0.5) between the two methods, with limits of agreement at -1.24 and 0.68. Lin's concordance correlation coefficient of absolute agreement was 0.91. Conclusion: The DH showed high sensitivity and diagnostic accuracy for anemia detection in PW, with substantial agreement with the hematology analyzer. It offers a convenient and rapid alternative for POC hemoglobin estimation in resource-constrained settings.

Abstract CT063: Phase Ib trial of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib (M4076) in patients (pts) with advanced solid tumors

Abstract Ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) protein kinases are critical in the DNA damage response. ATR and ATM genes have a synthetic lethal relationship in cancer and ATMi synergistically potentiates the efficacy of ATRi in vitro and in vivo. Here, we studied the combination potential of the highly potent, oral agents tuvusertib and lartesertib. The open-label, multicenter study DDRiver Solid Tumors 320 (NCT05396833) investigated safety, tolerability, PK and PD of tuvusertib + lartesertib in pts with advanced solid tumors refractory to standard therapy. PK samples were analyzed by a validated LC/MS method, and PD via γ-H2AX in ex vivo-stimulated CD45+ fraction by flow cytometry. As of 03.01.2024, 42 pts received ascending doses of tuvusertib + lartesertib. 5 pts experienced DLTs (Table 1). Frequent TEAEs (≥25 % of pts, any grade) were: anemia 62 %, nausea 45 %, fatigue and vomiting (43 % each). Grade ≥3 TEAEs occurred in 21 (50 %) pts; those in ≥3 pts were: anemia (n=9), decreased platelets (n=5), fatigue and decreased neutrophils (n=3 each). Preliminary steady-state PK showed rapid absorption: median Tmax of ~2-3 h (tuvusertib) and ~1-3.5 h (lartesertib); mean elimination half-life range of ~3.2-4.5 h (tuvusertib) and ~5.5-8.7 h (lartesertib); minimal accumulation. Exposure of the combination was consistent with respective monotherapies, indicating no clinically meaningful mutual drug-drug interactions. Preliminary PD showed complete or almost complete target inhibition 1-6 h after tuvusertib ≥130 mg and rebound above baseline after 24 h and target inhibition ~50 % across all time points at lartesertib ≥100 mg. 6 pts (2 ovarian, 2 uterine, 1 prostate cancer and 1 melanoma) had stable disease &amp;gt;16 weeks; 3 remain on treatment. Multiple tolerated combination doses were identified. Tuvusertib 180 mg QD + lartesertib 150 mg QD 2 w on/2 w off was selected for investigation in expansion cohorts in pts with prostate and endometrial cancer. Table 1. DLTs by ascending dose (DLT-evaluable patients) Dose (tuvusertib + lartesertib), mg N DLT DLT AE terms by cohort 2 w on/2 w off regimen 90 + 50 QD 3 No NA 130 + 50 QD 4 No NA 130 + 100 QD 3 No NA 180 + 100 QD 3 No NA 180 + 200 QD 4 Yes, in 2 pts One pt experienced febrile neutropenia Grade 3, neutrophil count decreased Grade 4, anemia Grade 3, platelet count decreased Grade 4, and candida infection Grade 2. The second pt had neutrophil count decreased Grade 4 180 + 150 QD 9 No NA 2 w on/1 w off regimen 180 + 150 QD 4 Yes, in 2 pts Both pts had platelet count decreased Grade 2 and Grade 3 180 + 100 QD 7 Yes, in 1 pt Neutrophil count decreased Grade 4 AE, adverse event; DLT, dose-limiting toxicities; N, DLT-evaluable patients; NA, not applicable; PD, pharmacodynamics; PCa, prostate cancer; PK, pharmacokinetics; pts, patients; QD, once daily, TEAE, treatment-emergent adverse event; w, week Citation Format: Lillian L. Siu, Elena Garralda Cabanas, Valentina Boni, Anthony W. Tolcher, Enrique Sanz Garcia, Jesús Fuentes-Antrás, Omar Saavedra, Deepthi S. Vagge, Giuseppe Locatelli, Burak Kürsad Günhan, Gregory Pennock, Jatinder Kaur Mukker, Ioannis Gounaris, Timothy A. Yap. Phase Ib trial of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib (M4076) in patients (pts) with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT063.

Abstract CT224: Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Abstract INTRODUCTION: Targeted α therapy (TAT) in mCRPC is a rapidly advancing class of radiotherapeutics that can effectively deliver potent and local radiation selectively to cancer cells while sparing the surrounding normal cells. Retrospective studies of 225Ac PSMA-RLT (radioligand therapy), have shown promise in pts with mCRPC, where activity correlates with disease characteristics and prior therapies. FPI-2265 (225Ac-PSMA-I&amp;T) consists of a small-molecule PSMA-targeting ligand coupled with a 225Ac radionuclide. Here we present the initial results from TATCIST, an ongoing, open-label, single-arm study (NCT05219500) to evaluate the efficacy and safety of FPI-2265 in pts with mCRPC that was initiated as an investigator-sponsored study then converted into an industry-sponsored trial with more stringent eligibility criteria. METHODS: Eligible pts are required to have progressive mCRPC with PSMA-positive PET. Prior radioligand therapy is permitted. Pts with skeletal metastases presenting as a superscan were excluded upon protocol amendment and excluded from this analysis. Four doses of FPI-2265 at 100 kBq/kg (±10%) are administered at 8-week intervals; de-escalation in cycle 2 and beyond is allowed. Proportion of pts with PSA ≤50%, maximum %PSA decrease, and safety and tolerability of FPI-2265 were assessed. RESULTS: At the time of the data cut (30Jan2024) 30 pts have received ≥1 dose FPI-2265, with 25 pts having ≥12 weeks follow up. For this analysis, 21 pts were evaluable for safety and 20 pts were evaluable for PSA response: 4 pts with superscan were excluded and 1 pt was excluded due to uninterpretable PSA data. In general, pts were heavily pretreated in terms of prior lines of therapy. Most pts (17/21 [81%]) had received a prior taxane, including 8 pts who received ≥2 lines of taxanes. Eight pts received prior 177Lu PSMA-RLT (Lu). PSA50 was achieved in 10/20 pts (50%); In a subset of pts with the baseline PSMA SUVmean &amp;gt;6 (n=13 overall; post-Lu, n=6), PSA50 was achieved in 9 pts (69%). Treatment-related adverse events (TRAEs) included dry mouth (18/21 [86%]), fatigue (10/21 [48%]) dry eye (6/21 [28%]), and anemia (6/21 [28%]). All were Grade 1-2 in severity, expect anemia Grade 3 which was observed in (5/21 [24%]). Other Grade 3 TRAEs included decreased platelet count (3/21 [14%]). No Grade 4 or 5 TRAEs were reported. Dry mouth was primarily Grade 1 (13/21 [62%]) with only 5 patients (24%) experiencing Grade 2 dry mouth; there were no related discontinuations. CONCLUSION: Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received prior Lu therapy. Higher PSMA SUVmean was associated with improved PSA responses, Safety and tolerability were consistent with other published studies of 225Ac-PSMA-RLTs. These initial results support further investigation of FPI-2265 and a new phase 2/3 trial will begin enrolling soon. Citation Format: Ebrahim S. Delpassand, Mohammad Jawed Hashmi, Julia Kazakin, Omer Nawaz, Gabriella Garufi, Joanne Schindler, Luke Nordquist. Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT224.

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: a single-centre retrospective study.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

Chronic renal insufficiency can cause early anemia: A cross-sectional study

Background: Chronic renal insufficiency has emerged as a global health issue, causing significant morbidity and mortality. Anybody can develop anemia but it is very common in people with chronic kidney disease (CKD). Renal anemia develops as a result of CKD, and its prevalence rises as the disease progresses. The WHO defines anemia as a hemoglobin level &lt;13 gm/dl for males as well as women in the post-menopausal age group and ˂12 gm/dl for women in the pre-menopausal age group. Aim and Objectives: This study was done to assess whether a correlation exists between the grades of anemia and various stages of chronic renal insufficiency. Materials and Methods: The authors conducted a cross-sectional study involving 145 subjects with diabetes mellitus and CKD. The primary aim was to investigate the various grades of anemia in different stages of CKD patients. We classified the CKD patients into 5 stages based on GFR rates, as defined by guidelines of the national kidney foundation. Results: This study shows that out of 145 subjects having diabetic nephropathy with CKD, 59 subjects had mild anemia, 60 subjects had moderate anemia, and 26 subjects had severe anemia. Data were analyzed using the SPSS 16.0 version. The qualitative results were presented in frequency, percentages, and graphs. Baseline characteristic cases were compared with grades of anemia. For the correlation between two variables, Pearson and Spearman correlation coefficients were applied. The majority of patients with Grade 2 and Grade 3 CKD had mildto-moderate grades of anemia which worsened as the stage of CKD progressed and came out to be highly significant. Conclusion: This study concludes that anemia is a consistent finding in patients of CKD; the severity of anemia progresses as the kidney function is compromised.

TO ASSESS THE ACCURACY AND RELIABILITY OF PALLOR IN THE ORAL CAVITY AND PALPEBRAL CONJUNCTIVA TO CLINICALLY DIAGNOSE ANAEMIA IN MIDDLE AGED FEMALE PATIENTS BY USING HAEMOGLOBIN AS THE REFERENCE STANDARD

Aim: To accurately determine the reliability of pallor on the dorsal surface of tongue and/or palpebral conjunctiva to diagnose anaemia in middle aged female patients, by using haemoglobin as the reference standard. To correlate pallor with different grades of anaemia according to WHO criteria. Objective: A cost effective chair side clinical observation of pallor to diagnose anaemia in middle aged female patients and to provide counselling thereby reducing the prevalence of anaemia and its associated morbidities, especially in poor resource setting. Method: Between 1st June 2022 to 30th Aug 2022, all female dental outpatients between 40-65 years of age were prospectively examined. Among these subjects,100 female patients with pallor on the dorsal surface of tongue and/or palpebral conjunctiva who met the specified inclusion and exclusion criteria, provided informed consent, and who had undergone blood test within one day of clinical pallor detection were enrolled in the study. Based on haemoglobin levels, anaemia was divided into mild, moderate, and severe according to WHO criterion (Hb: &lt;12g/dl). Anaemia was divided into mild (Hb: 11-11.99 g/dl), moderate (Hb: 7-10.99 g/dl), and severe (Hb: &lt; 7g/dl). Data was expressed as frequency and percentages. Result: In the present study, 82% of subjects with either conjunctival pallor or tongue pallor or both were anaemic with laboratory proven haemoglobin levels &lt; 12 g/dl which was found to be statistically significant. 14.6% subjects were diagnosed with mild anaemia, 51.2% with moderate anaemia, and 34.1% with severe anaemia. Among patients with mild and moderate anaemia, conjunctival pallor out performed tongue pallor whereas in subjects with severe anaemia, tongue pallor outperformed conjunctival pallor. Detecting pallor in a female patient is a dependable sign of anaemia. Furthermore, identifying tongue surface pallor is a strong signal of severe anaemia in female patients whereas conjunctival pallor is a good indicator for mild and moderate anaemia. The effective implementation of dietary counselling has the potential to significantly reduce the prevalence of anaemia.