Latest news with #FAERS
Medscape
08-05-2025
- Health
- Medscape
Lymphoma and CAR T–Related Renal Injury: Assessing the Risks
In the treatment of non-Hodgkin lymphoma with CD19 chimeric antigen receptor (CAR) T-cell therapy, baseline kidney function did not appear to be associated with an increased risk of developing acute kidney injury (AKI) from the treatment. However, other key factors, including low albumin, showed a link. 'Our study is the largest to date examining renal toxicity in CD19 CAR T–treated lymphoma patients,' senior author Roni Shouval, MD, PhD, director of the Precision Cellular Therapy Laboratory at Memorial Sloan Kettering (MSK) Cancer Center, New York City, said in an interview. While the findings show no link between baseline kidney function and the development of AKI, ultimately, 'hypoalbuminemia may be a better flag for AKI risk and a prompt for closer monitoring or proactive interventions such as fluid management and nephrotoxin avoidance,' Shouval said. The study was published in March in Haematologica . CAR T-cell therapy is known to provide durable disease remission in relapsed or refractory non-Hodgkin lymphoma, including in the disease subsets of large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). While the common treatment-related toxicities of cytokine release syndrome (CRS) and immune effector cell–associated neurologic syndrome (ICANS) are well documented, less has been reported regarding AKI treatment–related effects and outcomes. The US Food and Drug Administration Adverse Event Reporting System (FAERS) AKI Reports To investigate, Shouval, first author Alexander P. Boardman, MD, also of MSK, and colleagues first screened data from the FAERS database, identifying 5912 patients who had adverse events related to CD19 CAR T-cell therapy reported between January 2017 and September 2022. The patients had a median age of 62 years, and the most common CAR T-cell therapies utilized were axi-cel (n = 3526 patients), followed by tisa-cel (n = 1780), liso-cel (n = 178), and brexu-cel (n = 428). The main indications for CAR T-cell treatment were non-Hodgkin lymphoma (88%) and acute lymphoblastic leukemia (11%). Overall, 211 (3.6%) patients developed AKI that was determined to have a primary etiology of CD19 CAR T-cell therapy, with no significant differences based on age, sex, event year, type of CD19 CAR T-cell therapy, or indication. Of note, AKI was more common among patients treated with CD19 CAR T-cell therapy than among all other patients with cancer in the FAERS database (age- and sex-adjusted reporting odds ratio [ROR], 1.72). AKI developed at a median of 2.5 days post-infusion, and patients with AKI were more likely to have had concurrent CRS than those with other CAR T-cell reports not involving AKI (64% vs 50%; P < .001). The rates of life-threatening illness (22.75% vs 8.00%) and mortality (49% vs 23%; P < .001 for all) were higher among patients with AKI than among those with other CD19 CAR T-cell reports not involving AKI. 'In the FAERS dataset, we observed a disproportionately high reporting of AKI among CAR T recipients compared to other oncology patients, reinforcing that renal toxicity is a consistent safety signal on a population level,' Shouval said. A Closer Look In a subsequent single-center analysis, the authors identified 399 patients with relapsed or refractory non-Hodgkin lymphoma treated with CD19 CAR T-cell therapy at MSK Cancer Center between April 2016 and December 2023. Of the patients, 84% had LBCL, 11% had MCL, and 5% had non-LBCL. Their median age was 66 years, and the most common treatments included were axi-cel (46%), tisa-cel (20%), liso-cel (29%), and brexu-cel (5%). Of note, patients' pre-lymphodepletion estimated glomerular filtration rate (eGFR) was not associated with overall or progression-free survival, CRS grade ≥ 2, ICANS grade ≥ 2, or neutropenia. 'Thus, baseline renal function was not significantly associated with efficacy or toxicity endpoints,' the authors reported. AKI, Kidney Outcomes From the time of CAR T-cell infusion to day 100, AKI of any grade was reported among 39 (10%) of the MSK patients, with only a small percentage (5%) having grade ≥ 2 AKI. The majority of AKI cases (71.8%) were attributed to prerenal factors; 14 cases occurred concurrently with CRS. For survival outcomes, those developing AKI within 100 days of treatment had significantly lower progression-free survival (hazard ratio [HR], 2.63; P < .001) and overall survival (HR, 3.36; P < .001) than those without AKI. And among those with AKI grade ≥ 2, progression-free survival was significantly lower (HR, 3.14; P < .001), as was overall survival (HR, 4.18; P < .001). Low Albumin, Inflammatory Markers Linked to Increased AKI Risk Notably, after a multivariate adjustment, serum albumin level prior to lymphodepletion was a significant risk factor for AKI (HR, 0.15; P < .001). In addition, higher levels of inflammatory markers, specifically serum interleukin 6 (HR, 1.74; P = .008) and tumor necrosis factor alpha (HR, 2.23; P < .001), on day 0, just prior to CAR T-cell infusion, were significantly associated with the risk for AKI 'Intriguingly, we are the first to determine that hypoalbuminemia is strongly associated with risk of AKI after CAR T-cell therapy,' the authors reported. 'Hypoalbuminemia emerged as an even more robust independent predictor of AKI than baseline eGFR,' Shouval added. 'In clinical terms, we believe hypoalbuminemia is surrogate for frailty and possibly systemic inflammation,' he said. 'Therefore, patients with low albumin should be recognized as high risk for renal complications.' 'Overall, we find that most AKI events after CAR T-cell infusion are of grade 1 and that most patients recover from these events within 3 months,' the authors wrote. However, in looking at the eGFR and AKI outcomes together, Shouval concluded that 'these data position AKI as both a clinically meaningful and prognostically significant complication, deserving greater attention in the CAR T risk-benefit assessment.' Findings Point to a 'Cytokine-Driven Phenomenon' Commenting on the research, Michael D. Jain, MD, PhD, medical director of the Immune and Cellular Therapy Program at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, noted that the findings underscore that CAR T-cell therapy 'is really a cytokine-driven phenomenon rather than related to comorbidities that cause baseline chronic kidney disease [CKD].' He added that low albumin, often a marker of inflammation/cytokines, 'might contribute to AKI because it affects intravascular volume and thus blood flow to the kidney.' Jain agreed that the risk for AKI and other complications from CAR T is 'related more to tumor burden and inflammation than to baseline renal dysfunction.' 'In our center, we have protocols to give CAR T cells to patients who are on dialysis and believe we can safely deliver their therapy,' he noted. A Word of Caution Re CKD In a smaller study of 155 patients treated with CAR T-cell therapy for relapsed/refractory LBCL, a history of CKD was, contrarily, found to indeed be associated with AKI on a multivariate analysis (RR, 2.7; P = .04). However, while in Shouval's study, most patients who had low eGFR (< 60 mL/min/1.73 m2) received either liso-cel or tisa-cel, in this study, the majority of patients received axi-cel. Based on that, 'I would offer caution [using CAR T-cell therapy] in those with CKD, especially in those receiving axi-cel,' senior author Narendranath Epperla, MD, of the James Cancer Hospital, The Ohio State University, Columbus, Ohio, said in an interview. He added, however, that Shouval's research importantly 'highlights a clinically relevant yet understudied complication of CAR-T that would aid clinicians in decision-making and counseling peri-CAR T.'
Yahoo
31-03-2025
- Health
- Yahoo
Sotatercept FAERS study highlights emerging safety signals in PAH treatment
At the 2025 American College of Cardiology (ACC) meeting in Chicago, new real-world safety data were presented on sotatercept, a novel fusion protein for pulmonary arterial hypertension (PAH). A retrospective analysis of the FDA Adverse Event Reporting System (FAERS) revealed key adverse events (AEs) associated with sotatercept, including cerebrovascular accidents (CVAs), flushing, diarrhoea, neutropenia, and asthenia. The study emphasised a higher incidence of AEs in elderly patients (65–85 years), highlighting the need for vigilant monitoring in this population. PAH is a rare and progressive disease characterised by increased pulmonary vascular resistance, ultimately leading to right heart failure. Despite therapeutic advancements, PAH remains associated with high morbidity and mortality, necessitating the development of new disease-modifying agents. Sotatercept, a first-in-class activin signalling inhibitor, has demonstrated significant improvements in exercise capacity and haemodynamic parameters in clinical trials. However, its long-term safety profile in broader patient populations is still being evaluated. The FAERS analysis, which included 11 reported AEs as of June 2024, found that CVAs, flushing, diarrhoea, and neutropenia each accounted for 18.18% of reported cases. The age-based analysis revealed that 54.55% of AEs occurred in patients aged 65–85 years, with fewer incidents reported in younger cohorts. While no statistically significant differences were observed in AEs across organ system groups, the findings underscore potential safety concerns, particularly for elderly PAH patients. Key opinion leaders (KOLs) have previously emphasised sotatercept's transformative impact on PAH management. A European KOL noted: "Sotatercept is probably the most important development in PAH over the past ten years. It will change the complete treatment landscape and positioning of other compounds in the treatment algorithm." This statement highlights the significant clinical and commercial implications of sotatercept's entry into the PAH treatment paradigm. From a pharmaceutical strategy perspective, the FAERS findings introduce several critical considerations. First, the emergence of cerebrovascular events, although limited in frequency, may influence risk-benefit assessments during future regulatory reviews and labelling decisions. This could lead to targeted safety monitoring requirements or risk management plans (RMPs), particularly for older patients. Secondly, while sotatercept is positioned as an add-on therapy, the magnitude of its clinical benefits raises the possibility of earlier-line use. This could disrupt the current PAH treatment sequencing and challenge the market positioning of established endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors (PDE5is). Lastly, the real-world safety signals from FAERS may prompt payers to introduce stricter prior authorisation criteria or outcomes-based agreements, tying reimbursement to patient outcomes to mitigate potential safety risks. Despite the identified AEs, sotatercept's novel mechanism of action and clinically meaningful efficacy gains position it as a valuable addition to the PAH treatment landscape. As longer-term real-world data and larger post-marketing studies become available, the comprehensive safety profile of sotatercept will become clearer, helping to define its optimal role in PAH management. "Sotatercept FAERS study highlights emerging safety signals in PAH treatment" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
Yahoo
31-03-2025
- Health
- Yahoo
Sotatercept FAERS study highlights emerging safety signals in PAH treatment
At the 2025 American College of Cardiology (ACC) meeting in Chicago, new real-world safety data were presented on sotatercept, a novel fusion protein for pulmonary arterial hypertension (PAH). A retrospective analysis of the FDA Adverse Event Reporting System (FAERS) revealed key adverse events (AEs) associated with sotatercept, including cerebrovascular accidents (CVAs), flushing, diarrhoea, neutropenia, and asthenia. The study emphasised a higher incidence of AEs in elderly patients (65–85 years), highlighting the need for vigilant monitoring in this population. PAH is a rare and progressive disease characterised by increased pulmonary vascular resistance, ultimately leading to right heart failure. Despite therapeutic advancements, PAH remains associated with high morbidity and mortality, necessitating the development of new disease-modifying agents. Sotatercept, a first-in-class activin signalling inhibitor, has demonstrated significant improvements in exercise capacity and haemodynamic parameters in clinical trials. However, its long-term safety profile in broader patient populations is still being evaluated. The FAERS analysis, which included 11 reported AEs as of June 2024, found that CVAs, flushing, diarrhoea, and neutropenia each accounted for 18.18% of reported cases. The age-based analysis revealed that 54.55% of AEs occurred in patients aged 65–85 years, with fewer incidents reported in younger cohorts. While no statistically significant differences were observed in AEs across organ system groups, the findings underscore potential safety concerns, particularly for elderly PAH patients. Key opinion leaders (KOLs) have previously emphasised sotatercept's transformative impact on PAH management. A European KOL noted: "Sotatercept is probably the most important development in PAH over the past ten years. It will change the complete treatment landscape and positioning of other compounds in the treatment algorithm." This statement highlights the significant clinical and commercial implications of sotatercept's entry into the PAH treatment paradigm. From a pharmaceutical strategy perspective, the FAERS findings introduce several critical considerations. First, the emergence of cerebrovascular events, although limited in frequency, may influence risk-benefit assessments during future regulatory reviews and labelling decisions. This could lead to targeted safety monitoring requirements or risk management plans (RMPs), particularly for older patients. Secondly, while sotatercept is positioned as an add-on therapy, the magnitude of its clinical benefits raises the possibility of earlier-line use. This could disrupt the current PAH treatment sequencing and challenge the market positioning of established endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors (PDE5is). Lastly, the real-world safety signals from FAERS may prompt payers to introduce stricter prior authorisation criteria or outcomes-based agreements, tying reimbursement to patient outcomes to mitigate potential safety risks. Despite the identified AEs, sotatercept's novel mechanism of action and clinically meaningful efficacy gains position it as a valuable addition to the PAH treatment landscape. As longer-term real-world data and larger post-marketing studies become available, the comprehensive safety profile of sotatercept will become clearer, helping to define its optimal role in PAH management. "Sotatercept FAERS study highlights emerging safety signals in PAH treatment" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
USA Today
28-02-2025
- Health
- USA Today
What are the 'nicotine hiccups' and why do they happen?
What are the 'nicotine hiccups' and why do they happen? Show Caption Hide Caption Warning about Zyn nicotine pouches Zyn nicotine pouches are being called "gas station Ozempic.". But using these nicotine pouches can be addictive and possibly hazardous to your health. Fox - 5 Atlanta "Nicotine hiccups" sound made up. But experts say they're a real phenomenon. Recent data on drug side effects found that nicotine was associated with the hiccups, according to a 2021 study looking at the Food and Drug Administration's adverse-event reporting system (FAERS). And anecdotal evidence shows many nicotine users can relate, said Melissa Little, director of the Center for Nicotine and Tobacco Research at the University of Virginia School of Medicine. On TikTok, Reddit and elsewhere online, Zyn users and people who vape are comparing notes on their "niccups." "Why do Zyns and nicotine pouches give me hiccups every time?" TikTok user @callmecarolyn asked her followers, before cutting to a scene of her hiccuping in bed. Well, here's why. More: FDA seeks to limit nicotine in cigarettes, most cigars. Vapes and Zyn are excluded. Nicotine acts by binding to receptors in the brain and nervous system, Little said. When these receptors are activated, they release neurotransmitters throughout the body. One of these neurotransmitters, called dopamine, plays a role in regulating the phrenic nerve, which controls breathing in the diaphragm. 'Instead of them doing what they usually do, they get a little messed up and get activated in certain ways,' Little said. 'And that can induce hiccups.' Nicotine can also irritate the mucus membrane that aligns the throat and esophagus, which can lead to hiccups, she said. It can also stimulate stomach acid production and can cause reflux, triggering more hiccups. The Centers for Disease Control and Prevention says nicotine is a highly addictive substance found in tobacco products, such as cigarettes, and nicotine replacement therapies, like nicotine gum. Tobacco use among middle and high school students has decreased from 2023 to 2024, predominately due to a decline in e-cigarette use, according to the 2024 Annual National Youth Tobacco Survey. However, nicotine pouch use saw a slight uptick from 1.5% in 2023 to 1.8% in 2024. Sales also increased from 126 million pouches in August 2019 to 808 million in March 2022, according to the CDC. Nicotine pouches, sometimes referred to as 'lip pillow' or 'upper decker,' are placed between the lip and gum, according to the American Lung Association. They're similar to snus, which are oral pouches containing shredded tobacco leaf, except nicotine pouches contain nicotine powder. They come in several flavors and are available at different nicotine strengths. Zyn is the only brand of nicotine pouches that has received marketing authorization for many of its products for consumers 21 and older. The agency said in a statement that Zyn products pose a lower risk of cancer and other serious health conditions than cigarettes and most smokeless tobacco products due to substantially lower amounts of harmful constituents. Nicotine in adolescence can harm the parts of the brain that control attention, learning, mood and impulse control, the CDC said. Contributing: Reuters. Adrianna Rodriguez can be reached at adrodriguez@
