Monitoring Of Adverse Events Research Articles

Kidney Injury in Patient with Non-small-cell Lung Cancer Receiving Tepotinib.

We herein report a 68-year-old man with advanced non-small-cell lung cancer treated with tepotinib who showed marked general edema, hypoalbuminemia, and an elevated serum creatinine level. Although tepotinib-induced kidney injury due to creatinine transporter inhibition has been reported, renal biopsy findings suggested tubulointerstitial injury due to decreased renal blood flow, likely secondary to refractory fluid retention. This case highlights the potential for true kidney injury during tepotinib therapy and underscores the importance of careful monitoring and management of adverse renal effects.

Samelisant (SUVN-G3031), A Histamine 3 Receptor Inverse Agonist: Results from The Phase 2 Double-Blind Randomized Placebo-Controlled Study for The Treatment of Excessive Daytime Sleepiness in Adult Patients with Narcolepsy

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5% patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

The WHO Algorithm for Causality Assessment of Adverse Effects Following Immunization with Genetic-Based Anti-COVID-19 Vaccines: Pitfalls and Suggestions for Improvement

Clarifying and differentiating the causes of diseases is an essential step in any clinical activity, but it takes on particular relevance and complexity in the case that arise following vaccinations. The WHO has proposed a protocol that uses a list of specific questions about vaccine-related adverse events and an algorithm for making a judgement. Here, we analyze and discuss the important limitations of this protocol when applied to the new genetic-based anti-COVID-19 vaccines, particularly once dealing with rare and unexpected pathological events. The main controversial aspects concern: (a) the prevailing consideration of other possible causes; (b) the biological plausibility and the choice of an appropriate time window to consider adverse effects possibly caused by vaccines; (c) the reference to scientific literature, which may be very limited and often controversial in early stages of introducing new vaccines because of the short period of observation; (d) the final classification of the algorithm into only three classes, which leaves ample space for the “indeterminate” category. Failure to address these issues may lead to distorted pharmacovigilance reports with significant consequences on the benefit/harm assessment. In anticipation of possible future pandemics managed with new vaccines, the WHO algorithm needs to be revised with appropriate protocols for monitoring and evaluation of adverse effects that take into account the novel mechanism of action and real-world epidemiological data.

Real-world study of adverse events associated with triptan use in migraine treatment based on the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS) database

BackgroundTriptans selectively agoniste 5-Hydroxytryptamine(5-HT) receptors and are widely used in the treatment of migraine. Nevertheless, there is a dearth of comprehensive real-world clinical research on the safety of triptans. In light of the growing prevalence of migraine, it is imperative to gain a deeper understanding of the true extent of adverse events (AEs) associated with triptans in the clinical management of migraine.MethodsA database query of AEs reported to the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for triptans was performed using the online platform Open Vigil 2.1. The query spanned the period from 1 January 2018 to 31 December 2023 and extracted all AEs for ‘sumatriptan’, ‘zolmitriptan’, ‘rizatriptan’, and ‘naratriptan’ from the 15–49 years old population and retrospective quantitative analyses. A proportional reporting ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) methodology were utilized to contrast AEs across the four triptans.ResultsA total of 1.272 AEs reports for sumatriptan, 114 for zolmitriptan, 162 for rizatriptan, and 15 for naratriptan were identified. The ratio of females to males was approximately three times higher in all cases, with the highest number of reports originating from the Americas. A review of the FAERS database revealed that nervous system disorders were the primary SOC category for four drugs, with all four drugs exhibiting the AE indicative of reversible cerebral vasoconstriction syndrome, also classified as Nervous system disorders. The most frequently reported AE signal for sumatriptan was dyspnea, which is classified as respiratory, thoracic and mediastinal disorders. The most frequently reported AEs signals for the remaining three drugs were nausea, vomiting and terminal ileitis, all of which are classified as gastrointestinal disorders.ConclusionAnalyses have demonstrated that AEs are present in a range of systems, including cardiac, nervous, gastrointestinal, and musculoskeletal disorders. It should be noted, however, that the incidence and signal intensity of these AEs vary depending on the specific drug in question. In clinical practice, the selection of an appropriate drug and the monitoring of AEs should be tailored to the individual patient’s and specific characteristics.

Implementation of a lisocabtagene maraleucel chimeric antigen receptor T-cell therapy outpatient monitoring program: Multicenter nursing/advanced practice provider perspectives

ObjectivesLisocabtagene maraleucel (liso-cel; Breyanzi), an autologous chimeric antigen receptor T-cell therapy, has demonstrated efficacy and safety in relapsed/refractory large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma. Outpatient monitoring after liso-cel administration has shown lower health care resource utilization and cost and high patient satisfaction. However, outpatient monitoring programs require well-designed processes with collaborations from multiple stakeholders across several facilities. The study objective is to provide learnings and key considerations from nurses and advanced practice providers (APP) with experience setting up and managing liso-cel outpatient monitoring programs. Data sourceAuthor experience gathered from 3 institutions at 2 workshops. ResultsIn the reviewed programs, patients are discharged on the same day after liso-cel infusion and observation. They are required to remain within a short distance of the facility for ≥4 weeks with admission to treatment facilities upon experiencing adverse events (AE). Nurses/APPs report several key features of successful programs: flexibility to carry out essential roles/functions based on institution's resources and staff structure, a phased or hybrid (hospital/clinic) approach to program launch, a core team to run and guide the program, robust training for staff, options to tailor AE monitoring based on institution guidelines, and coordinated transitions between multiple stakeholders and facilities. ConclusionsNurses/APPs are critical contributors to liso-cel outpatient monitoring programs. Success in providing appropriate, complex individualized care in these programs can be achieved by using a multistakeholder approach with appropriate staff and patient/caregiver training and careful coordination across multiple functions and facilities. Implications for nursing practiceThe learnings and resources presented may provide insight to considerations around the development of a cell therapy outpatient monitoring program. However, the information provided here should be taken together with other relevant resources and guidelines and should be adapted to align with the institution's own guidelines.

Immune checkpoint inhibitor-induced pancreatic enzyme elevation in melanoma patients: Incidence, management and therapy-A multicentre analysis.

Immune checkpoint inhibitors (ICI) are considered standard-of-care in the systemic treatment of melanoma. However, management of certain ICI-associated adverse events (AE) can be challenging. Incidence, course and management of immune checkpoint inhibitor-induced pancreatic injury (ICIPI) are not well-documented and specific diagnostic and therapeutic algorithms are lacking. Current management includes serological monitoring of pancreatic enzymes, radiographic imaging and corticosteroid or further immunosuppressive treatment. Based on previous data regarding adjuvant ICI treatment, we suspected that elevation of pancreatic enzymes may occur more frequently than reported while the clinical relevance of-particularly asymptomatic-ICIPI is still unclear. A collaboration of eight Austrian and Swiss dermato-oncology centres was established to retrospectively analyse a large cohort of ICI-treated patients regarding incidence and management of ICIPI. Additionally, a questionnaire-based survey concerning ICIPI-management was conducted. Among 1516 melanoma patients receiving ICI therapy, 204 patients exhibited ≥CTCAE II° lipase elevation. Of these patients, 41 (20.1%) had symptoms suggestive of pancreatitis. Immunotherapy was interrupted or discontinued due to pancreatic AE in almost half of the patients. Systemic corticosteroids were administered in 103 patients (50.5%), with higher doses reported in symptomatic cases. Six per cent of asymptomatic patients had radiographically proven pancreatitis. Maximum lipase elevation was >5xULN in all of these patients. Routine lipase monitoring was conducted in all participating centres, although not recommended in respective guidelines. Elevation of serum lipase was observed more frequently than recently reported. Although radiographic findings indicating pancreatitis were rare in asymptomatic patients, ICI treatment was frequently paused or discontinued and systemic steroids were administered. To reduce the existing uncertainty in routine clinical practice reflected by our findings, we provide an algorithm to guide the monitoring and management of potential pancreatic adverse events. Lipase measurement should be limited to symptomatic patients and/or those with radiographic findings indicative of pancreatic injury.

Long-Term Efficacy and Safety of Risankizumab for csDMARD-IR Patients With Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 1 Trial

Introduction &amp; Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 from the KEEPsAKE 1 trial. Materials &amp; Methods: The ongoing KEEPsAKE 1 clinical trial is a global, phase 3, multicenter study to evaluate the efficacy and safety of RZB versus placebo (PBO) in patients with active PsA. Patients are at least 18 years old and demonstrated an inadequate response, intolerance or contraindication to ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Following a 24-week double-blind, PBO-controlled, parallel-group treatment period (period 1), all patients received open-label RZB every 12 weeks thereafter (period 2). Safety assessments were based on monitoring of treatment-emergent adverse events (TEAEs) reported as events per 100 patient-years (PY). Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug. Results: Overall efficacy results were maintained at week 196 of the KEEPsAKE 1 trial, as compared to previously reported timepoints. At week 196, 39.4% of patients receiving continuous RZB and 38.1% of PBO/RZB patients achieved ACR50; 39.6% of RZB and 35.2% of PBO/RZB patients achieved MDA. In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 65.2% on RZB and 62.9% on PBO/RZB achieved PASI90 at week 196. mNAPSI and PGA-F scores improved from baseline by 14.99 and 1.5 points, respectively, for RZB, and by 14.73 and 1.5 points for PBO/RZB patients. In patients with enthesitis at baseline, 60.1% on RZB and 63.4% on PBO/RZB achieved resolution. For patients with dactylitis at baseline, 72.3% on RZB and 77.6% on PBO/RZB achieved resolution. HAQ-DI (RZB -0.40, PBO/RZB -0.33), SF-36 PCS (RZB 8.98, PBO/RZB 7.21) and FACIT-Fatigue (RZB 7.7, PBO/RZB 5.6) scores maintained improvement from baseline to week 196. The overall rates of TEAEs (121.4 E/100PY), serious TEAEs (7.7 E/100PY) and AEs leading to discontinuation of study drug (1.8 E/100PY) have remained stable and comparable to those reported in period 1. Conclusion: The 196-week results of the ongoing KEEPsAKE 1 trial demonstrate the durable efficacy of RZB 150 mg in treating the different clinical manifestations and improving health-related quality of life in csDMARD-IR patients with PsA. RZB continued to be well-tolerated, with no new safety signals.

Electronic patient-reported outcomes as digital therapeutics for patients with cancer: a narrative review of current practices and future directions.

Improved cancer treatment outcomes have increased the demand for medical care that considers the quality of life of patients with cancer. Patient-reported outcomes (PROs) help assess the quality of life because they involve direct evaluation of the patients. Recently, electronic PROs (ePROs) have been used in clinical cancer care settings in Europe and the United States. Electronic PROs positively affected communication between patients with cancer and healthcare providers, enhanced education, optimized self-management, contributed to healthcare economics, assisted in monitoring adverse events, and improved prognosis. However, challenges such as adherence, burden on healthcare providers, lack of personalized formats, low digital literacy, and implementation costs remain. Therefore, carefully selecting the items to be recorded by ePROs in alignment with specific objectives is essential. Additionally, developing systems using lifelogs-digital records of daily activities-and creating mechanisms that automatically encourage patient behavioral changes based on the reported data are crucial. This review delineates the advantages and challenges of ePROs according to their history and proposes the prospects of ePRO.

Factors influencing participation of elderly population in mass drug administration for lymphatic filariasis: a cross-sectional study.

The success of mass drug administration (MDA) for lymphatic filariasis (LF) elimination relies on achieving a participation rate of at least 65% within the endemic community. However, participation of sub-population in the community varies and a significant treatment gap among the elderly population, remains to be addressed. The present study explores the factors influencing the elderly participation in MDA and propose possible solutions to bridge the gap. A cross-sectional study of individuals aged 60years and above was conducted from August to December 2023 in Yadgiri district of Karnataka, which is endemic for LF. The participants were interviewed using a structured questionnaire, focusing on the perception about LF and MDA and drug consumption behaviours. STATA 14 software was used to analyse the data. We used a logistic regression model to determine the factors influencing drug consumption. The study included 315 elderly individuals with a mean age (SD) of 67.4 (6.2) years. Although, 58.4% of them received the drugs during the last round of MDA in 2023, only 40.6% consumed it. The drug refusal rate was 19.4%. Fear of side effects (22.9%) was cited as the primary reason for not accepting the drugs. Weak perception of LF transmission risk (25.7%) and mistrust of drug safety (42.5%) were reported as reasons for non-compliance. Logistic regression identified significant associations, including residence (peri-urban: OR = 6.80), chronic disease (diabetes: OR = 2.89), trust on drug safety (OR = 16.27), and opinion of neighbours (OR = 5.35). Participation of elderly population in MDA was suboptimal (40.6%). Tailored interventions to improve consumption such as addressing misconceptions, building trust in MDA and effective monitoring and management of adverse events are vital to enhance their participation. The National Programme should have specific guidelines and strategies to address this issue to improve their participation in MDA for elimination of LF.

The Use of Cefiderocol in Gram-Negative Bacterial Infections at International Medical Center, Jeddah, Saudi Arabia.

The necessity for ground-breaking treatments for Gram-negative infections is evident. The World Health Organization, the Infectious Diseases Society of America, and the European Commission have highlighted the critical insufficiency of efficient antibiotics, urging pharmaceutical businesses to manufacture new antibiotics. Therefore, developing new antibiotics with broad efficacy against Gram-negative pathogens is essential. Thus, this research aimed to evaluate the safety and effectiveness of cefiderocol in treating multidrug-resistant Gram-negative bacterial infections at the International Medical Center (IMC), Jeddah, Saudi Arabia. A retrospective analysis was conducted on patients treated from January 2021 to February 2023. Thirteen case groups treated with cefiderocol were compared to twenty control groups treated with other antibiotics. The results indicated no statistically significant differences in ICU stay, comorbidity indices, or mortality rates between the two groups. Cefiderocol showed high clinical and microbiological cure rates, despite the severity of the patients' conditions. Carbapenem-resistant Klebsiella pneumoniae and difficult-to-treat resistance Pseudomonas aeruginosa were the most prevalent pathogens in the case and control group, respectively. Two patients treated with cefiderocol developed Clostridioides difficile infection, emphasizing the need for close monitoring of potential adverse effects. The results of this study support cefiderocol as a viable alternative for managing serious infections instigated by multidrug-resistant Gram-negative bacteria.

The efficacy and safety of addition of pegylated interferon to long-term nucleos(t)ide analogue therapy on functional cure of chronic hepatitis B patient: a systematic review and meta-analysis.

This meta-analysis aims to assess the efficacy and safety of adding pegylated interferon (Peg-IFN) to long-term nucleos(t)ide analogs (NAs) treatment for achieving functional cure in patients with chronic hepatitis B (CHB). This meta-analysis was registered in PROSPERO (CRD42024519116). We searched PubMed, Embase, Cochrane Library and Web of Science for randomized controlled trials that compared adding Peg-IFN to long-term NAs with NAs alone for the treatment of CHB. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model. Seven trials with 692 participants were included. Compared to NAs monotherapy, sequential combination therapy significantly increased the HBsAg seroclearance rate (RR 4.37, 95%CI: 1.92-9.55; I2 = 0%) and HBsAg seroconversion rate (RR 3.98, 95%CI: 1.50-10.54; I2 = 0%), and the results reached statistical significance. Compared to NAs monotherapy, sequential combination therapy showed a significant increase in HBeAg seroclearance rate (RR 2.04; 95%CI: 0.47-8.82; I2 = 73%) and HBeAg seroconversion rate (RR 2.10; 95%CI: 0.41-10.71; I2 = 67%), but did not reach statistical significance. Sequential combination therapy was more likely to experience adverse events. Although most reactions are mild and reversible, vigilant monitoring for treatment-related adverse events is essential, with prompt intervention when needed. For CHB patients on long-term NAs treatment, sequential combination therapy boosts HBsAg seroclearance and HBsAg seroconversion rates compared to monotherapy. However, it may increase adverse events. Additional studies are needed to thoroughly evaluate its clinical effectiveness, given the current limited research available. PROSPERO, identifier CRD42024519116.

Ensuring safety and monitoring adverse events in clinical trials: Challenges and innovations

Safety and adverse events (AEs) monitoring in clinical trials are critical to ensuring participant safety and the successful development of new therapies. Effective monitoring not only protects patients but also helps identify any risks associated with the investigational product. This paper elaborates on the methodologies used to detect, categorize, and report adverse events during clinical trials, and how these processes are governed by stringent regulatory frameworks. Additionally, the discussion highlights the role of pharmacovigilance systems, the ethical obligations researchers face in AE reporting, and the technological innovations that are transforming safety monitoring. Challenges, including under-reporting, data variability, and interpretation difficulties, are examined in depth. Ultimately, advancements in real-time data collection, adaptive trial designs, and artificial intelligence (AI) are promising to improve the accuracy and timeliness of adverse event monitoring, shaping the future of clinical research and patient safety.

Predictors of abemaciclib discontinuation in patients with breast cancer: a multicenter retrospective cohort study

ObjectiveThis study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer.Material and MethodsBetween November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to discontinuation for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis.ResultsBaseline weight < 54 kg, bone metastases, and hemoglobin level ≤ 12.4 g/dL were independent predictors of abemaciclib discontinuation for any reason. The main adverse events leading to abemaciclib discontinuation were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight < 54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea.ConclusionPatients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment discontinuation. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.

Cooling and physiology during parent cuddling infants with neonatal encephalopathy in usual care: CoolCuddle-2 study.

CoolCuddle, enabling parents to cuddle their babies with neonatal encephalopathy (NE) during therapeutic hypothermia and intensive care (TH), was developed in research settings. To determine the impact of implementing CoolCuddle in usual care in six diverse neonatal intensive care units on the cooling process and intensive care. This vital sign cohort study embedded within the CoolCuddle implementation study enrolled 36 infants receiving TH for NE. Nurses received training on CoolCuddle and a standard operating procedure using an instruction video. After consenting, parents experienced up to 2 h of CoolCuddle with 30 min of pre- and post-cuddle observation. We used multilevel, clustered linear modelling to assess the physiological stability in temperature, cardio-respiratory and neurophysiology across the CoolCuddle. In 60 CoolCuddles over 93.12 h, respiratory parameters, heart rate or neurological function did not vary between the epochs (p > 0.05). During cuddle, sleep-wake cycling on amplitude-integrated EEG increased (p = 0.008) and there was weak evidence of lower pain scores (p = 0.08). No adverse effects were observed. Implementing CoolCuddle with support in usual practice maintained physiological stability and did not significantly affect the cooling process or intensive care, and may improve infant comfort. Ongoing monitoring of adverse effects when implementing CoolCuddle is recommended.

Immune-related and Common Adverse Events With Programmed Cell Death 1/Programmed Cell Death Ligand 1 inhibitors combined with other Anticancer Therapy for Solid Tumors: A Systematic Review and Meta-analysis

AimsThe combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors and anticancer therapies has been in the spotlight in recent years. However, the risks associated with these combination therapies are not fully elucidated. The primary objective of this study was to evaluate the relative risk of organ-specific immune-related adverse events (irAEs) and common adverse events (AEs) in patients treated with PD-1/PD-L1 inhibitor–based combination therapies compared to those treated with PD-1/PD-L1 inhibitor monotherapy for solid tumors. Materials and methodsAn electronic database search was performed using ClinicalTrials.gov, Medline, and American Society of Clinical Oncology (ASCO)/European Society for Medical Oncology (ESMO) annual meeting libraries. We included randomized controlled trials designed to assess the safety of combination therapies using PD-1/PD-L1 inhibitors and other anticancer drugs. All the selected clinical studies included solid tumors and provided information on the incidence of nonserious and serious AEs. The quality of evidence was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using random-effect models to pool the results. ResultsThe primary analysis included 16 relevant clinical studies comprising 4232 patients, of whom 2071 and 2161 patients received PD-1/PD-L1 inhibitor–-based combination therapy and PD-1/PD-L1 inhibitor monotherapy, respectively. Serious organ-specific irAEs were infrequent, even when PD-1/PD-L1 inhibitors were combined with other anticancer drugs. The incidence of serious colitis was significantly higher in the combination therapy group than in the monotherapy group. Among the common AEs associated with PD-1/PD-L1 inhibitors, the incidence of serious pyrexia/fever, nonserious pyrexia/fever, fatigue, nausea, decreased appetite, vomiting, diarrhea, dyspnea, and rash significantly increased in the combination therapy group. In the subgroup analysis based on the modes of action of concomitant anticancer drugs, the combination of PD-1/PD-L1 inhibitors and DNA synthesis inhibitors significantly increased the risk of serious colitis compared to PD-1/PD-L1 inhibitor monotherapy. ConclusionOrgan-specific irAEs occur infrequently when combinations of PD-1/PD-L1 inhibitors and other anticancer drugs are used. However, the risk of serious colitis and certain AEs is higher than that associated with PD-1/PD-L1 inhibitor monotherapy. Vigilant monitoring of AEs and implementation of appropriate clinical management strategies guided by the mode of action of the combination drugs are essential.

Managing Select Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors.

The increased use of immune checkpoint inhibitors (ICIs) across cancer programs has created the need for standardized monitoring and management of immune-related adverse events (irAEs). Delayed recognition without appropriate treatment can have serious and life-threatening consequences. The management of irAEs presents a unique set of challenges that must be addressed at a multidisciplinary level. Although various national and international guidelines and working groups provide high-level recommendations for the management of irAEs, practical guidance is lacking. Furthermore, timely collaboration between specialists requires institutional protocols that enable the early recognition, assessment, and treatment of irAEs. Such protocols should be developed by institution specialists and include algorithms for all healthcare providers involved in the care of patients treated with ICIs. At William Osler Health System in Brampton, Ontario, practical step-by-step multidisciplinary treatment approaches with recommendations for the management of irAEs were developed in collaboration with experts across Canada. Here, we provide an in-depth description of the approaches, outlining baseline investigations prior to the initiation of ICIs, as well as the monitoring and management of irAEs based on symptoms, severity, and involved organ systems. We encourage other centres to adapt and modify our approaches according to their specific needs and requirements.

Role of Immunotherapy in Non-Small Cell Lung Cancer (NSCLC)

Background: Non-small cell lung cancer accounts for approximately 85% of all lung cancers and presents a serious public health challenge due to an increasing incidence and poor prognosis, with only a 5-year survival rate of 5-10% in advanced disease stages. Objective: The aim of this work is an overview of the clinical efficacy and safety profile of ICIs in NSCLC patients, mainly focusing on the predictive role played by PD-L1 expression and tumor mutational burden as predictive biomarkers of treatment response. Methods: A total of 63 NSCLC patients treated with ICIs at a Department of Respiratory Medicine, Dhaka National Medical Institute Hospital, Dhaka, Bangladesh and National Institute of Diseases of the Chest and Hospital (NIDCH), and National Institute of Cancer Research &amp; Hospital (NICRH), Mohakhali, Dhaka, Bangladesh from July 2023 to December 2023, were retrospectively analyzed. Demographical information, treatment regimens, and clinical outcomes were collected and analyzed. Treatment responses were evaluated based on Response Evaluation Criteria in Solid Tumors, and safety was assessed through monitoring adverse events. Results: The median age of the cohort was 62 years, with presentation in advanced stages, III and IV in 70%. An objective response rate of 42% was observed; median PFS was 8.5 months. Of note, patients with high PD-L1 expression of ≥ 50% had a response rate of 60%, whereas those with lower expression had a rate of 30%. It was observed in TMB analysis that high mutational burden is associated with a median PFS of 10 months versus 5 months in the case of low TMB. About 15% of patients developed adverse events, mostly immune-mediated. Conclusion: This study has exemplified the promising efficacy of ICIs in the improvement of treatment outcomes for patients with NSCLC and underlined critical roles that PD-L1 expression and TMB have played in guiding personalized treatment strategies. Although encouraging, these findings are retrospective and ..

Managing Adverse Events in Clinical Trials with R and Shiny

Adverse events (AEs) are critical occurrences that can significantly impact patient safety and the overall success of clinical trials. Effective management of AEs is essential for ensuring regulatory compliance and safeguarding participants' well-being. This paper explores the integration of R and Shiny as innovative tools for the real-time monitoring, visualization, and analysis of AEs in clinical trials. By leveraging R’s robust statistical capabilities and Shiny’s interactive interface, researchers can enhance data management processes, facilitate informed decision- making, and foster collaboration among stakeholders. A case study is presented to illustrate the practical application of R Shiny in tracking AEs, demonstrating its effectiveness in improving trial outcomes and ensuring patient safety. The findings emphasize the need for adopting dynamic data analysis tools to optimize adverse event management in the evolving landscape of clinical research. KEYWORDS Adverse Events, Clinical Trials, R, Shiny, Data Management, Visualization, Real-Time Monitoring, Patient Safety.

Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications.

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

8812 Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center Retrospective Study

Abstract Disclosure: N.B. Luna: None. E. Mendoza: None. S.A. Kho: None. Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center, Retrospective Study Immune checkpoint inhibitors (ICIs) serve as immunomodulatory antibodies, which enhance the immune system and substantially improve the prognosis for patients with advanced malignancies [1]. Referral to endocrinology have been increasing because ICIs were associated with endocrine-related adverse effects including hypothyroidism, hyperthyroidism, diabetes, hypophysitis and adrenalitis. Hence, the study aimed to retrospectively determine the local prevalence and profile of Filipino patients who developed endocrinopathies during ICI therapy at the University of Santo Tomas Hospital (USTH), Manila, Philippines from 2013-2019. A single-center retrospective study of ICI-treated cancer patients with serial biochemical and/or radiologic monitoring of endocrine adverse effects was done upon approval by the Research Ethics Committee. A total of 27 subjects were included with a median age of 60 years and male predominance. Pembrolizumab consisted 93% of the ICIs given. The incidence of thyroid dysfunction was 36% (18% overt hypothyroidism, 9% subclinical hypothyroidism, and 9% subclinical hyperthyroidism). The median time at risk for development of overt hypothyroidism is 4 weeks with median TSH level of 9.05 uIU/mL from baseline level of 3.77 uIU/mL. All patients who had baseline hypothyroidism worsened with increase from baseline levothyroxine dose by 50 to 230% in order to achieve euthyroidism (p 0.037). Serial monitoring was done every 2 weeks until euthyroidism. ICIs were temporarily put on hold in 75%. Diabetes (p 0.05), renal carcinoma (p 0.001) and dose of 200mg (p 0.42) were associated to developing overt hypothyroidism. Checking of glycemic levels was not routine among non-diabetic patients. Fifteen percent of diabetic patients had worsening of control (median HbA1c 8.5% [8-9] and 23% were newly diagnosed pre-diabetes (median fasting glucose 114mg/dL [104-120]). With the available imaging results, there were no abnormal adrenal metabolic uptake on PET scan and no evidence of hypophysitis in pituitary MRI. In conclusion, overt hypothyroidism is a common occurrence during ICI therapy (18%). Worsening occurred among all patients with hypothyroidism at baseline. New-onset pre-diabetes and worsening of glycemic control were seen in 15 and 23%, respectively. Serial clinical and biochemical monitoring is important and referral to endocrinology should be made if deemed necessary. [1] L Agrawal, A Bacal, S Jain, V Singh, N Emanuele, Ma Emanuele &amp; F Meah (2020) Immune checkpoint inhibitors and endocrine side effects, a narrative review, Postgraduate Medicine, 132:2, 206-214, DOI: 10.1080/00325481. 2019. 1709344 Presentation: 6/1/2024