Citations

ABSTRACT We describe a case of immunoglobulin A nephropathy (IgAN) treated with targeted-release budesonide (Nefecon) that resulted in notable systemic adverse effects. The patient developed cushingoid features, weight gain, hyperglycaemia and leucocytosis within 3 months of therapy. During dose tapering he experienced symptomatic adrenal insufficiency confirmed by low morning cortisol, requiring hydrocortisone replacement. Despite Nefecon’s design for terminal ileum absorption, and hence assumed minimal systemic exposure, this case demonstrates clinically significant adverse effects and adrenal suppression. These findings underscore the need for careful monitoring and patient education when initiating and tapering Nefecon in IgAN management.

Abstract Patients with multiple myeloma have an elevated risk of severe complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) infection. To demonstrate proof of concept for a pandemic preparedness and response network, the American Society of Hematology Research Collaborative Multiple Myeloma Program developed a prospective, decentralized study within a site-based provider network. In the COVID-19 outcomes in myeloma and the impact of vaccines (COSMIC) study, patients provided consent, permitted electronic health record data collection, completed patient-reported outcomes at baseline, day 30, and day 180 through an electronic study portal, and were compensated for participation. Clinicians at participating sites facilitated study recruitment and shared best practices monthly to accelerate study execution. The COSMIC study rapidly consented 201 patients from 8 participating sites over 4 months (22 January 2024 through 17 May 2024). Consented participants were 30 to 93 years old, with a median age of 67; 46% were female, 69% were non-Hispanic White, 17% were non-Hispanic Black, and 8% were Hispanic/Latino. Patient-reported data completion was 97% at baseline, 81% at 1 month, and 79% at 6 months. At baseline, 55% of patients reported a history of COVID-19 infection and had received a median of 4 SARS-CoV-2 vaccines. For all patients, there were an additional 18 COVID-19 infections and 57 vaccines received during the 6-month observation period. There were no significant differences in health-related quality of life over time or by history of COVID-19 infection. COSMIC demonstrates the feasibility of an innovative evidence generation strategy to drive rapid accrual of patients to address an evolving area of need. This trial was registered at www.clinicaltrials.gov as #NCT05831787.

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are nephroprotective but are associated with early eGFR decline, also termed “eGFR dip.” Despite elevated risk of kidney disease, this phenomenon is understudied among people with HIV (PWH). Methods: In a 1:1 propensity score–matched cohort study using data from 9 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites, we compared new SGLT2i users with new users of other antihyperglycemic classes. We estimated adjusted hazard ratios (aHRs) for time to ≥10% and ≥30% eGFR decline using multivariable Cox proportional hazards models and analyzed eGFR change using multivariable linear mixed models. In addition, longer-term eGFR trends over 24 months were visualized using locally weighted scatterplot smoothing (LOWESS) curves. Results: Among 1554 eligible PWH, we obtained 295 matched pairs. Over 6 months, eGFR decline incidence of ≥10% and ≥30% was higher among users of SGLT2i versus other antihyperglycemic classes (58.2% vs. 37.4%; aHR: 1.79; 95% CI: 1.40%–2.28%; and 17.3% vs. 9.8%; aHR: 1.69; 95% CI: 1.05–2.73; respectively). The adjusted mean eGFR change at 6 months was −2.62 mL/min/1.73 m 2 for SGLT2i versus 0.05 mL/min/1.73 m 2 for other classes. Long-term eGFR trends revealed an expected initial decline after SGLT2i initiation, followed by stabilization and a slower subsequent decline compared with other classes. Conclusions: Acute eGFR dips were more common among PWH initiating SGLT2i relative to other antihyperglycemic classes, although overall declines were small, transient, and consistent with the general population. Further research is needed to explore the long-term effects of SGLT2i in PWH.

Kidney dysfunction after heart transplantation (HT) is associated with significant morbidity and mortality. Recipient and perioperative factors may all influence the risk of kidney injury. Furthermore, data suggest that the incidence of kidney dysfunction, both acute and chronic, is increasing after the implementation of the United States’ 2018 allocation system due to increasing use of temporary mechanical circulatory support and changing recipient characteristics. While data are robust regarding nephroprotective therapies such as renin-angiotensin-aldosterone system inhibition and SGLT2i (sodium-glucose cotransporter 2 inhibitors) to minimize the progression of chronic kidney disease in patients with heart failure, data in HT recipients are beginning to emerge. This state-of-the-art review will critically examine the existing literature regarding the epidemiology of kidney dysfunction after HT, mitigation strategies for acute kidney injury and chronic kidney disease, including pharmacotherapeutics, the need for kidney transplantation after HT, and practical next steps for the larger HT community.

Abstract Background: Survivor plots permit adjustment by baseline demographics and clinical characteristics; log-normal survival analysis may be more robust than a Cox model under departures from model assumptions. We depicted distant disease-free survival (DDFS) for statistically standardized quantitated ER, PgR, and HER2. Methods: We utilized CCTG MA.27 (NCT00066573), an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumours. IHC ER, PgR, and HER2 HSCORE were centrally assessed by machine image quantitation, and statistically standardized to mean of 0, standard deviation (SD) of 1 following Box-Cox variance stabilization transformations of square for ER, natural logarithm (ln) and square root for PgR, and ln for HER2. For the ln transformation, 0.1 was added to 0 HSCOREs for a stable transformation. The primary endpoint was DDFS at the longest trial follow-up of 4.1 years. For log-normal survival analysis, ln(time) is a linear function of covariates and had a normal distribution; the Cox models were log-linear for covariates. Survival was depicted with log-normal and Cox survivor plots adjusted at the means of age, T and N stage, grade, lymphovascular invasion, treatment, and baseline patient demographics. We examined ER and PgR ASCO/CAP cut-points at (0; >0), HER2 cut-points at (IHC 0, 0 stain; IHC 0, (0,10%] stain; IHC 1+; IHC 2+; IHC 3+), and ER/PgR/HER2 standardized cut-points at standard deviations about mean of 0 (<-1; (-1,0]; (0,1]; >1). P was based on the likelihood ratio criterion (∼Χ2 (1)) for the addition of ER/PgR/HER2 to the model of baseline covariates, and had nominal significance if P<0.05. Log-normal and Cox multivariable regressions with unstandardized and standardized categorical, and continuous, ER, PgR, and HER2 were adjusted by baseline covariates; 2-sided Wald tests had nominal significance if P<0.05. Results: Of 7576 MA.27 patients, 2325 patients had quantitated image analysis assessments for ER, PgR, and HER2; 113 of 2325 (4.9%) patients experienced a DDFS event during follow-up. Multivariable log-normal survival analysis indicated DDFS was significantly longer for patients with T1 (p=0.01), N0 (p=.002), and grade 1/2 tumors (p=0.01); similar significance levels were found with a Cox model. Log-normal survivor plots were smooth, while Cox survivor plots were step-wise discontinuous at events. Adjusted log-normal survivor plots indicated similar 5-year DDFS for patients by standardized ER categories (p=0.43): 95.4% for those with ER <-1.0 (n=401); 95.8%, for (-1.0,0.0] (n=737); 96.1%, for (0.0,1.0] (n=737); and 96.4%, for >1.0 (n=450). The log-normal standardized PgR survivor plots indicated patients had significantly different 5-year DDFS (p<.001) by categories, with both ln and square root transformations of HSCORE: with a ln transformation, 93.7% for <-1.0 (n=607); 95.4%, for (-1.0,0.0] (n=390); 96.8%, for (0.0,1.0] (n=826); and 97.8%, for >1.0 (n=502). Patients had similar 5-year DDFS by standardized HER2 categories (p=0.71): 96.2% for <-1.0 (n=83); 96.0%, for (-1.0,0.0] (n=1201); 95.9%, for (0.0,1.0] (n=527); and 95.7%, for >1.0 (n=514). In full fit multivariable log-normal survival analyses, DDFS was not significantly different for ER (p=0.51-0.89) and HER2 (p=0.12-0.98); higher PgR was associated with significantly better DDFS (p=0.01 to <.001). Adjusted Cox survival analyses had similar results. Conclusions: Survivor plots adjusted for baseline demographic and clinical characteristics provided similar indications of significance for standardized ER, PgR, and HER2 as those seen in multivariable models with both log-normal and Cox survival analyses. Higher PgR was associated with significantly better DDFS. Citation Format: J. W. Chapman, J. Bayani, S. SenGupta, J. M. S. Bartlett, T. Piper, M. A. Quintayo, S. Virk, P. E. Goss, J. N. Ingle, M. J. Ellis, G. W. Sledge, G. T. Budd, M. Rabaglio, R. H. Ansari, R. Tozer, D. P. D'Souza, H. Chalchal, S. Spadafora, V. Stearns, E. A. Perez, K. A. Gelmon, T. J. Whelan, C. Elliott, L. E. Shepherd, B. E. Chen, K. J. Taylor. Survivor plots for quantitated adjunctive statistically standardized ER, PgR, and HER2 in adjuvant postmenopausal breast cancer: Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-07-23.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14–28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable across treatment arms and reflected both pathogen blooms as well as less severe disruptions of the microbial community. Clostridium scindens and secondary bile acid metabolism pathways were less prevalent in the PTCy arm than in the Tac/MTX arm post-HCT, yet presence of secondary bile acid metabolism pathways was associated with a lower risk of chronic GVHD. Given that PTCy was associated with a greater disruption of the microbiome as measured by diversity, absolute microbial abundance, and bile acid metabolism capability, but better clinical outcomes overall, these data suggest that the importance of the microbiome in modulating the host immune systems after allo-HCT is specific to different types of GVHD prophylaxis.

Background: A summary of pharmacist-based practices and preferences regarding the prevention and management of high-dose methotrexate (HDMTX) toxicity in patients with lymphoma does not exist. The objective of the study was to describe current practices surrounding management of HDMTX therapy. This was done through a self-administered, web-based, cross-sectional survey of hematology/oncology pharmacists to ascertain practices and individual attitudes about HDMTX therapy management. Responses were summarized with descriptive statistics. Response comparisons were made using Chi-square or Fisher’s exact test for categorical data, and Kruskal-Wallis test for variables on the Likert scale. A total of 175 pharmacists provided 116 eligible surveys [68 (59%) complete responses and 48 (41%) partial responses] for analysis. The Cockcroft-Gault estimated creatinine clearance formula was the most preferred method (61%) to estimate kidney function and determine HDMTX dosing. Respondents would proceed with HDMTX therapy until the predicted risk of AKI, or AKI stage 2 or 3, exceeded 50% and 20%, respectively. Preferred treatment modifications for a high predicted AKI risk after HDMTX exposure included additional prehydration, HDMTX dose reduction, and increased kidney function monitoring, although levels and degrees of agreement varied. Respondents indicated that serum cystatin C-based GFR estimates lacked evidence, accuracy, and practicality in HDMTX therapy management. There was limited familiarity with cell cycle arrest biomarker use during HDMTX therapy. Glucarpidase was considered time-sensitive and highly effective; however, acquisition cost represented a barrier to use, and the optimal dose was felt to be unknown. In conclusion, there is significant heterogeneity in supportive practices and beliefs about the optimal management for patients with lymphoma receiving HDMTX therapy.

Objectives: To summarize recent high-quality trials and provide an update to the original 2022 American College of Radiology Appropriate Use Criteria for Treatment of Locoregional Gastric Adenocarcinoma. This multi-specialty-led committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and surgical oncology. Methods: Using the population, intervention, comparator, outcome, timing, and study design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective Phase II/II trials and select retrospective studies published between 5/1/2020 and 8/1/2025 in the Embase, Medline, and Pubmed databases. Study type and quality were assessed. Well-established RAND-UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Results: ARS AUC recommendations include adjuvant FLOT chemotherapy for localized gastric adenocarcinoma after neoadjuvant FLOT and surgery, poCT or perioperative chemoimmunotherapy for localized gastric adenocarcinoma, adjuvant chemotherapy +/− CRT for localized gastric adenocarcinoma that undergoes upfront surgery, and systemic therapy alone for localized gastric adenocarcinoma in a medically inoperable patient. Conclusions: This updated ARS AUC summary provides guidelines for the multimodality treatment of resectable gastric adenocarcinoma.

Abstract Objective To assess the role of small‐molecule calcitonin gene–related peptide receptor antagonists (gepants) in the acute treatment of migraine, particularly in relation to triptan treatments. Background Triptans have established efficacy and are widely prescribed for the acute treatment of migraine. However, triptans may not be recommended for some individuals due to cardiovascular contraindications and precautions, as well as other comorbidities, and many may discontinue triptans because of inadequate or inconsistent symptom relief or poor tolerability. Several gepants are also indicated for the treatment of migraine (both acute and preventive), and their demonstrated efficacy and safety may address some challenges associated with triptans. Methods This narrative review addresses considerations for the acute treatment of migraine through summarizing literature and data from preclinical studies and clinical trials of triptans and gepants. Results We consider triptans and gepants, where available, first‐line treatment options for the acute treatment of migraine. Triptans may be prescribed in the absence of contraindications, significant risk of cardiovascular disease, or risk for or history of medication‐overuse headache. In those who have contraindications or precautions for triptans, those who do not have an adequate response to triptans, and those unable to tolerate them, gepants are often an appropriate option. The efficacy and safety of gepants for the acute treatment of migraine has been established through clinical trials and open‐label extension studies and based on real‐world evidence. Gepants have demonstrated efficacy and tolerability in triptan insufficient responders, perhaps because of their distinct mechanisms of action. Additionally, the safety of gepants, including relative cardiovascular safety, is supported in pivotal controlled trials and open‐label extension trials. In experimental settings and through their use as preventive treatment for migraine, gepants appear unlikely to produce medication‐overuse headache. In addition, one gepant (ubrogepant) has demonstrated efficacy in preventing headache onset when given during the prodrome, a finding that has not been demonstrated for triptans. A single‐arm, open‐label study of naratriptan given during the prodrome suggested fewer subsequent headaches, but interpretation is limited because there was no contemporaneous control group. Limited head‐to‐head clinical trials comparing gepants and triptans have not demonstrated significant differences. Prescribers of both triptans and gepants should be mindful of potential drug–drug interactions. Conclusions Key advantages of gepants include their favorable tolerability, efficacy for the acute treatment of both the prodromal/premonitory phase (ubrogepant) and the headache phase of migraine (ubrogepant, rimegepant, zavegepant), lack of cardiovascular contraindications, and lack of association with medication‐overuse headache. Disadvantages include limitations due to cost and access and CYP3A4 drug interactions for most gepants. Together, the advantages may help to optimize patient care and lead to better persistence and effectiveness in a real‐world setting. Head‐to‐head studies are needed to clarify the comparative effectiveness of triptans and gepants.

ABSTRACT Purpose Active lesion expansion is clinically important because it can indicate disease progression and influence management and treatment planning. However, sequential imaging is often unavailable, and rapid growth can only be inferred from indirect findings such as active perilesional tissue injury. This study aimed to implement and test the feasibility of an MR elastography (MRE)‐based technique for assessing the expansile nature of mass lesions by detecting stiffness changes caused by mechanical strain manifestations in adjacent tissues. Methods A tissue strain mapping (TSM) algorithm was developed using spatial–temporal directional filtering to reveal the presence of perilesional latent strain that is not apparent in conventional MRE inversions. The technical feasibility was tested in tissue‐simulating phantoms containing a mass that was progressively expanded. Preliminary feasibility for clinical application was also demonstrated in representative in vivo examples. Resulting TSM maps were compared with conventional MRE stiffness maps. Results In the phantom experiments, TSM revealed the presence of local strain at the periphery of the expanding mass, with the effect increasing proportionally to the degree of expansion. Conventional MRE did not demonstrate comparable localized stiffening patterns. In vivo examples showed similar perilesional strain features that were not apparent on conventional MRE maps. Conclusion The feasibility of the proposed MRE‐based TSM technique was demonstrated in phantom and preliminary in vivo studies. These findings suggest that the technique is a promising tool for assessing the expansile nature of mass lesions and motivate further development of the TSM processing and exploration of potential clinical applications.