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Abstract Background/rationale Primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia (Post-PV/ET MF) (collectively termed MF) are chronic hematopoietic malignancies with progressive bone marrow collagen fibrosis, peripheral cytopenias, extramedullary hematopoiesis, splenomegaly, debilitating constitutional symptoms and heightened risk of transformation to acute leukemia. The only currently approved therapies for MF are JAK inhibitors (JAKi) which can provide significant improvements in splenomegaly and systemic symptoms but do not fundamentally change the pathogenesis of the disease. As a result, additional non-JAKi therapies for patients with MF after JAKi failure represent an important translational focus. Reparixin is a novel, potent and specific inhibitor of the chemokine CXCL8 (IL)-8. IL-8 is a member of a class of cytokines involved in leukocyte recruitment and activation in tissues. There are two known types of CXCL8 receptors – CXCR1 and CXCR2, which are expressed in neutrophils (Baggiolini M, Adv Immunol 1994). IL-8/CXCR1/2 signaling has been shown to be a key mediator of inflammatory signaling in MF patients. Hematopoietic stem/progenitor cells from patients with MF are enriched for a CXCL8/CXCR2 gene signature and display enhanced proliferation and fitness in response to an exogenous CXCL8 ligand in vitro. Genetic deletion or a small molecule inhibitor of CXCR2 in MF mouse adoptive transfer models ameliorates fibrosis, extends overall survival and improves hematologic parameters (Dunbar A, Blood 2023). This pre-clinical data validates targeting this pathway in clinical investigations. Study design This is an open-label, phase II study assessing the efficacy, safety, and tolerability of reparixin in patients with Dynamic International Prognostic Scoring System (DIPSS) intermediate-2, or high-risk PMF, post ET/PV MF either after prior treatment with, or those who are ineligible for treatment with a JAKi. Patients will receive oral reparixin 1200 mg three times daily on a four-week cycle for a core study period of 24 weeks. Patients who achieve at least clinical improvement (CI) or stable disease (SD) with one grade improvement in bone marrow fibrosis by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria at the Cycle 7 response assessment may continue receiving reparixin until loss of response, disease progression, unacceptable toxicity, patients/physician withdrawal, or termination of study by sponsor. The study monitors both efficacy and toxicity using a Bayesian Optimal Phase 2 (BOP2) design. If response is observed in at least one patient out of 10 and safety is confirmed at the interim analysis, the trial will proceed to full enrollment of 26 patients. If more than three responses are observed in the total cohort, then a signal of activity is confirmed. Primary Objective: To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF. Secondary Objectives: To assess the efficacy of reparixin as determined by response assessment using IWG-MRT/ELN criteria at the end of Cycle 6 and Cycle 12. To assess the change in bone marrow fibrosis grade at the end of Cycle 6 and Cycle 12 with reparixin. To assess the safety of reparixin as measured by the adverse event profile of Common Terminology Criteria for Adverse Events v5.0. To assess spleen volume reduction by imaging after Cycle 6 and Cycle 12 as compared to baseline spleen volume. Key Exploratory Objectives: To evaluate changes in quality of life and patient-reported outcomes To conduct correlative studies to measure biomarkers of reparixin activity, such as Vascular Endothelial Growth Factor (VEGF) levels, bone marrow microvessel density, megakaryocyte number and peripheral blood CD34+ cell number, and patients with and without IL-8 secretion. Key inclusion criteria: Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the WHO diagnostic criteria with intermediate-2 or higher risk disease by DIPSS Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy Have adequate liver and kidney function Platelet count ≥ 25 x 109/L Bone marrow and peripheral blood blast count < 10% ANC ≥ 1000 mm3. MPN Research Consortium (MPN-RC) 120 is currently enrolling patients through the MPN-RC clinical sites throughout the United States. Clinical Trial Identifier NCT05835466

Abstract Background In patients with myelofibrosis (MF) undergoing allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD) prophylaxis has traditionally included a calcineurin inhibitor (CNI) plus methotrexate (MTX). We conducted a retrospective study comparing the safety and efficacy of post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to CNI-based regimens. Methods This study was approved by the Mayo Clinic IRB. Patients with myelofibrosis who underwent allo-HCT after 2016 at Mayo Clinic in Arizona and Florida were included. Categorical variables were compared using Chi-square or Fisher's exact tests. Overall survival (OS) was defined from transplant to death, and progression-free survival (PFS) from transplant to relapse or death. OS and PFS were estimated using Kaplan-Meier methods; univariate differences were assessed with log-rank tests. The cumulative incidence of acute and chronic GVHD and time to neutrophil and platelet engraftment were analyzed using competing risk models, with death as a competing event; differences were tested using Gray's test. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Results A total of 110 patients were included. 53 patients received PTCy-based prophylaxis (43 PTCy/Tac/MMF, 1 PTCy/CSA/MMF, 9 PTCy/Siro/MMF), while 57 received non-PTCy regimens (54 Tac/MTX +/- 39 T-cell depletion, 2 CSA/MMF, 1 Tac/MMF). Median age at transplant was 63 (range: PTCy 40-76; others 38-74) years in both groups; 59 were male (58.5% PTCy vs 49.1% others). Median Karnofsky Performance Status (KPS) and HCT–Comorbidity Index (HCT-CI) in patients receiving PTCy vs non-PTCy were 90 vs 80 and 1 vs 3, respectively. Conditioning intensity was similar: 22.6% myeloablative vs 21.7%, and 77.4% reduced-intensity vs 76.7% in PTCy and non-PTCy, respectively (p=1.000). Stem cell source was peripheral blood in all patients except one in the non-PTCy group who received bone marrow. 58 patients had primary MF (54.7% PTCy vs 50.9% others), and 52 had secondary MF (45.3% PTCy vs 49.1% others), including essential thrombocythemia (28.3% PTCy vs 31.6% others), polycythemia vera (17.0% vs 15.8%), and MPN-NOS (0% vs 1.8%). Median follow-up was 26.2 months (95% CI: 20.7-52.7) in the PTCy and 60.6 months (95% CI: 53.1-70.6) in the non-PTCy cohort. CD3 and CD33 donor chimerism ≥95% at day +100 was 66.7% and 86.7% in PTCy vs 63.6% and 92.7% in others, respectively (p=0.50); day +100 driver molecular mutations were present in 32.1% of PTCy and 32.0% of others (p>0.99). Rates of acute GVHD grades ≥2 and ≥3 were not statistically significant, in the PTCy group (37.7% vs 49.1% p=0.229 and 17.0% vs 22.8% p=0.445, respectively). Chronic GVHD (any grade) occurred in 42.3% of PTCy vs 38.2% of others (p=0.664), while moderate-to-severe cGVHD was lower with PTCy (21.2% vs 27.3% p=0.461). Platelet engraftment was significantly delayed in the PTCy group (median 33 vs 21 days, p=0.030). Median time to neutrophil engraftment was also delayed in the PTCy group (20 vs 17 days, adjusted p=0.025). Age-adjusted HR for time to platelet engraftment was 0.60 (95% CI: 0.41–0.90; p=0.014), and for neutrophil engraftment 0.65 (95% CI: 0.44–0.95; p=0.025), indicating significantly delayed hematopoietic recovery with PTCy. Graft failure occurred in 9.4% vs 5.3% (p = 0.48); primary 7.5% vs 3.5%, secondary 1.9% vs 1.8% in PTCy vs non-PTCy groups, respectively. Relapse or progression occurred in 11.3% of PTCy vs 17.5% of others (p=0.355); four patients in the non-PTCy group progressed to AML post-transplant, versus none in the PTCy group (p=0.119). 1-year TRM was 22.6% in the PTCy group and 14.0% in the non-PTCy group, p = 0.324. Median OS was 72.8 months in the PTCy group (95% CI: 49.9 months, upper limit not estimable [NE]) and 93.4 months in the non-PTCy group (95% CI: 48.5 months, upper limit NE), although the difference was not statistically significant (p=0.739). After adjusting for age and HCT-CI, there were no significant differences in PFS (adjusted HR 1.37; 95% CI: 0.73–2.56; p=0.331) or OS (adjusted HR 1.27; 95% CI: 0.64–2.51; p=0.498). Conclusions In myelofibrosis patients undergoing allo-HCT, PTCy-based GVHD prophylaxis showed similar rates of grade ≥2 acute and moderate-severe chronic GVHD compared to non-PTCy regimens. Engraftment was significantly delayed, while OS and PFS were comparable. PTCy appears to be a safe and viable alternative to CNI-based prophylaxis.

Abstract Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) for which the only approved therapies are JAK inhibitors which improve splenomegaly and disease-related symptoms. Inflammatory pathways beyond JAK-STAT are critical in the pathobiology of MF and contribute to patients' clinical manifestations. IL-1β is a master regulator of inflammation which is overexpressed in MPNs, preferentially supports the MPN mutant stem cell, and interacts with key cytokines that are implicated in fibrogenesis, inflammatory symptoms, and disease progression. Knockout of IL-1β in MPN mouse models led to an abrogated clinical phenotype, while pharmacologic inhibition of IL-1β resulted in reduction of reticulin fibrosis and osteosclerosis. Canakinumab is a fully human monoclonal antibody that binds to and neutralizes IL-1β. It is approved for rare inflammatory disorders with a safety profile that has been extensively studied in the CANTOS trial that assessed cardiovascular outcomes in high-risk patients (pts). Based upon these data, we designed a phase 2 study of canakinumab in pts with MF. Methods NCT05467800 is a Myeloproliferative Neoplasm Research Consortium (MPN-RC) ongoing open-label, 2-part, phase 2 study of canakinumab in pts with MF. Part 1 enrolled pts with MF previously treated with or ineligible to receive a JAK inhibitor. Canakinumab was given subcutaneously at a dose of 200mg on day 1 of 21-day cycles. Primary response assessment occurred at week 24 following cycle 8. Responding pts could continue to receive canakinumab. Eligible pts had platelets >25 x109/L and a need for MF-directed therapy defined as ≥ 1 of the following: hemoglobin <10 g/dL, transfusion dependency, splenomegaly palpated ≥ 5cm below left costal margin, and/or MPN-SAF version 4.0 TSS ≥ 10. The primary endpoint was overall response rate (ORR) including CR, PR, or CI after 8 cycles (24 weeks). A Bayesian optimal phase 2 (BOP2) design was used with an interim analysis performed after 10 pts. Results In part 1, 14 pts were enrolled and 13 were treated. One pt discontinued prior to starting treatment due to rapidly progressive disease. Enrollment onto part 1 has closed with 2 pts remaining on treatment. Median age was 70 y (range: 55-83). Eleven (84.6%) pts had received prior ruxolitinib. Median hemoglobin was 8.2 g/dL (range: 5.7-13.2), median platelet count was 114 x 109/L (range: 21-484), and median WBC was 9.7 x 109/L (range: 2.4-71.4). Five (38.5%) pts were transfusion dependent. Median MF-SAF TSS at baseline was 15 (range: 4-46). Median spleen volume at baseline was 1522 cm3 (range: 362cm3-2997cm3). Pts received a median of 9 cycles (range: 2-19). Three (23%) pts responded at week 24, achieving a CI-symptom response (TSS50). Six (46%) pts experienced progression of disease due to spleen volume increase. Median hemoglobin was 8.2 g/dL at baseline, 7.9 g/dL at week 12, and 9.0 g/dL at week 24. Median platelet count was 114 x 109/L at baseline, 98 x 109/L at week 12, and 183 x 109/L at week 24. Median MF-SAF TSS declined from 15 at baseline to 10 at week 12 and 9 at week 24. Eleven (85%) pts exhibited symptom improvement during treatment (MF-SAF TSS percent change from baseline range -20% to -85%). In pts with baseline hsCRP ≥ 1.0 (n = 8), canakinumab led to a reduction at week 24 (or EOT if prior to week 24) in 5/8 (62.5%) with a median decrease in CRP of 37%. The most common adverse events (AEs) were anemia and thrombocytopenia and often attributed to underlying disease. Non-hematologic grade ≥ 3 AEs occurred in 3 pts and were deemed unrelated to canakinumab, except for one grade 3 increase in bilirubin that was possibly related per the treating physician. Conclusion The IL-1β inhibitor, canakinumab, resulted in consistent symptom improvement and exhibited beneficial impact on cytopenias in pts with R/R MF while demonstrating a manageable toxicity profile. Consistent with pre-clinical data, inhibition of IL-1β had little impact on splenomegaly, an observation that was likely enhanced by frequent JAK inhibitor discontinuation prior to study start. Given the encouraging impact on MF symptoms, blood counts and reassuring safety profile, the study was amended to enroll pts on a stable dose of a JAK inhibitor (ruxolitinib, fedratinib, momelotinib, or pacritinib) who have the potential to benefit from additional therapy. Part 2 is currently enrolling at multiple sites and updated clinical and correlative data will be presented at the meeting.

Abstract BACKGROUND Cognitive symptoms are common among cancer patients treated with intracranial radiation but inadequately assessed and suboptimally treated, owing in part to the time-consuming and resource-intensive nature of formal neuropsychological testing. Through remote administration of brief cognitive assessments and symptom-directed interventions, decentralization uniquely addresses this problem. METHODS In this single-site phase 2 fully decentralized clinical trial (NCT06377696), patients treated with radiation therapy (RT) for primary or metastatic brain tumors undergo cognitive evaluations with the application, Mayo Test Drive, and the Short Test of Mental Status (STMS; via telehealth or in person), at baseline and every three months for one year. Participants are provided wearable devices for health promotion. Half the participants are randomized to metformin to evaluate this agent’s efficacy in treating RT-related cognitive symptoms. Target enrollment is 100 participants. RESULTS Seventy-three patients (median age 45.5, 46% female) with brain tumors who received RT were enrolled May 2024 to May 2025. In this unplanned interim analysis, we evaluated the impact of decentralization on study participation. Thirty-six participants (49%) reported a primary residence greater than 150 miles from our institution. Seven patients were consented remotely, the remainder in person. Of 380 study-related visits (201 STMS, 179 treatment toxicity checks) 216 (57%) were completed by telehealth. Thirty-two of 336 (9.5%) study-related lab draws were completed at locations outside our institution. Wearable device data was continuously collected, with median 3022 steps tracked per patient per day on study. 190/250 (76%) quality-of-life surveys sent digitally were completed to date. CONCLUSION Decentralization implemented as part of this clinical trial enabled participation despite significant distance from our institution and facilitated study-related assessments through digital solutions, eliminating the need for travel. Our findings demonstrate the feasibility of conducting a fully decentralized supportive care trial in neuro-oncology, which can increase participation and accelerate evaluation of novel therapeutics.

Abstract BACKGROUND Access to in-person evaluations is challenging for patients with glioma due to disease-related disability and distance from specialized neuro-oncology centers. Telehealth is an alternative to in-person evaluations, but acceptability of and therapy compliance with this model has not been prospectively evaluated. METHODS In this single-arm non-randomized pragmatic clinical trial, we compared patient satisfaction with telehealth and in-person assessments among patients with glioma undergoing chemotherapy with temozolomide. Participants acted as their own controls, alternating between telehealth and in-person visits. Patient satisfaction with care delivered was evaluated by Press-Ganey surveys with Likert response scales (1-5, 1=very poor, 5=very good). A digital pill diary (DPD) was implemented to track chemotherapy compliance. RESULTS We accrued 30 patients (median age 59, 38% female) between October 2024 and May 2025. Half of the patients (n=15) reported a primary residence greater than 150 miles from our institution. Surveys from 25 participants were reviewed, with 17/25 completing one or more surveys following an in-person visit, and 21/25 completing one or more surveys following a telehealth visit. Overall average Press-Ganey scores were similar between the two visit modalities with high scores (telehealth=4.8; in-person=4.7). Median scores for specific modalities were similarly highly rated: likelihood of recommending practice to others (telehealth=5.0; in-person=5.0), concern the care provider showed (telehealth=5.0, in-person=4.7), provider’s discussion of treatment options (telehealth=5.0, in-person=5.0), provider effort to include patients in decision-making (telehealth=5.0, in-person=5.0). DPDs used to monitor treatment compliance indicated adherence to all prescribed doses of temozolomide in 75/79 cycles; the other 4 (of 79) treatment cycles were halted per provider instructions. CONCLUSION This interim assessment demonstrates feasibility of treating patients with similar patient satisfaction of care delivered between telehealth and in-person visits. The DPD was effective in tracking chemotherapy administration. Additional results including visit type preference and acute care utilization data are maturing.

Abstract The Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) was developed by the US National Cancer Institute to allow patients to directly report their side effects, enhancing the accuracy and patient‐centeredness of cancer clinical trial adverse event reporting. Clinician‐based reporting often misses the full range of patient symptoms, resulting in underreporting of side effects. The selection of adverse events for patient reporting must be defined in advance and consistently applied across all study arms. Investigators can use core symptom sets, including diarrhea, fatigue, and nausea, alongside tailored items specific to the treatments being studied. PRO‐CTCAE has demonstrated similar scores across electronic, paper‐based, and automated telephone administration methods. PRO‐CTCAE administration typically occurs before start of treatment and regularly throughout treatment, with the administration frequency tailored to the expected trajectory of side effects. Ensuring high survey completion rates is essential for PRO‐CTCAE success. Standard reporting can include tabular reporting of the proportion of patients with any (score ≥1) and high (score ≥3) levels of symptoms at the individual item level. A baseline‐adjustment approach should be applied to account for symptoms before start of treatment to isolate treatment‐emergent adverse events. The distribution of PRO‐CTCAE scores at each time point can be visualized using stacked bar charts. PRO‐CTCAE integration into cancer clinical trials is crucial for capturing a comprehensive range of treatment‐related symptomatic adverse events and improving the evaluation of therapy tolerability. Ongoing research continues to refine its implementation, supported by regulatory guidance.

Background/Objectives: Autoimmune inner ear disease (AIED) causes sensorineural hearing loss that classically presents as fluctuating, asymmetric loss of hearing. Associated vestibular and other ear symptoms can be present in many patients. First-line treatment of AIED is high-dose corticosteroids. AIED can present either as a primary condition limited to ear involvement or secondary, as part of an underlying systemic autoimmune rheumatic disease, the most common of which include vasculitis and relapsing polychondritis. We described our cohort of primary AIED, including demographics, treatment, and outcomes. We excluded from this review sensorineural hearing loss in the context of vasculitis and relapsing polychondritis. Methods: We performed a chart review of patients with the diagnosis of AIED at Mayo Clinic and compared the cohort by sex. Results: Thirty-one patients met the inclusion criteria. The mean age was 48.5 years, and 17 were men. Patients were initially evaluated at the Department of Otorhinolaryngology or Internal Medicine, and 29 patients were subsequently referred to the Department of Rheumatology, with a mean of 12.2 weeks after the first evaluation. Treatment with corticosteroids showed improvement in hearing and vestibular symptoms during the first month but no further improvement by the end of the third month. Other immunosuppressive medications were used with various degrees of response. Methotrexate was the second most used therapy, with 11 of 17 patients reporting an improvement in symptoms. Conclusions: Corticosteroid therapy is an effective initial treatment for AIED and should be followed with corticosteroid-sparing agents to prevent further damage to the cochlea.

TPS2099 Background: Gliomas are the most common primary central nervous system (CNS) malignancy in adults, accounting for 26.3% of all brain tumors. Care at high volume centers is associated with an overall survival benefit, but access to in-person evaluations can be challenging due to disease-related neurological disability and loss of income. Telehealth represents a convenient and efficient alternative to in-person evaluations, but acceptability and comparative safety of this care delivery modality has not been prospectively evaluated among glioma patients undergoing chemotherapy. Methods: This single-arm non-randomized pragmatic clinical trial evaluates patient satisfaction with, and safety of video-enabled telehealth assessments compared to in-person evaluations for patients with glioma undergoing temozolomide chemotherapy. The study includes adult patients with a diagnosis of glioma requiring adjuvant temozolomide chemotherapy. Participants act as their own controls, alternating between in-person and telehealth assessments while undergoing chemotherapy dosed per standard of care. Monitoring labs are completed locally and transmitted electronically. For participants without access to Wi-Fi or a device (e.g. mobile phone or computer), cellular-enabled tablet devices are provided to facilitate appointments and completion of electronic study components. All participants who travel to in-person appointments are reimbursed for travel expenses. The primary outcome measure is patient satisfaction with care delivered, as measured by institutional Press-Ganey survey scores obtained following telehealth and in-person assessments. A key secondary outcome measure is completion rate of planned oral chemotherapy, tracked using a digital pill diary incorporated into our institutional electronic health record. The digital diary allows real-time tracking of chemotherapy adherence and adverse events experienced by participants. Other secondary outcomes include acute care utilization days following telehealth and in-person visits (defined as emergency department evaluations and days of inpatient stay), neurologic disability as measured by the Neurologic Assessment in Neuro-Oncology (NANO) scale, and disease related quality of life measured by the EORTC QLQ-C30. All participant surveys are self-reported and completed electronically. This decentralized pragmatic clinical trial provides unprecedented, prospective real-world data on utilization of telehealth services compared to in-person visits for patients undergoing chemotherapy for glioma. We expect the data generated to inform the design and conduct of future decentralized interventional neuro-oncology trials. NCT06625047 opened for enrollment in October 2024, 16 of 30 intended participants were accrued as of January 2025. Clinical trial information: NCT06625047 .

Context.— A monthly pathology journal club has met for 24 years. It was established to help members stay apprised of the literature relevant to diagnostic pulmonary pathology. Objective.— To assess whether the journal club met its goal and to report on opportunities identified for improvement. Design.— To determine whether articles chosen for discussion as opposed to notation were more significant, Scopus citation indices for article types reviewed from January 2007 to November 2023 were compared. A survey of current faculty was undertaken to determine if the club was meeting expectations and to identify improvement opportunities. Results.— Articles from January 2007 to November 2023 included 858 discussed and 3385 noted. Mean (SD) citation count was 103.0 (409.80) for discussion and 64.9 (259.77) for notation articles ( P < .001). The citation count was noticeably right skewed, as articles with high citation counts inflated the mean. Members were mostly satisfied with the way the journal club was structured and managed. Members most valued the summary of the articles, followed by the live discussion. Opportunities for improvement included decreasing the number of journals scanned, decreasing detail in summaries, and using generative artificial intelligence (AI) to facilitate summary generation. A pilot using AI anecdotally reduced preparatory time, but the human-edited summary included more specific context, critical commentary, and enhanced take-home messages, providing a more nuanced analysis. Conclusions.— The journal club met its initial goal. Opportunities for improvement have been identified including the use of generative AI to facilitate article summarization.

Objectives To compare postoperative complication rates of patients with metabolic syndrome (MetS) with patients without MetS after holmium laser enucleation of the prostate (HoLEP) for management of benign prostatic hyperplasia (BPH). Patients and Methods We retrospectively reviewed patients aged >40 years who underwent HoLEP at our institution from 2007 to 2022. Criteria for MetS were diagnoses of at least three of the following: diabetes mellitus, hypertension, hyperlipidaemia, or obesity (body mass index ≥30 kg/m 2 ). Uni‐ and multivariable logistic regression were used to compare the likelihood of immediate, 30‐day, and 90‐day complications between groups. Results A total of 1500 patients were included with a median (interquartile range) age of 70 (65–76) years. Patients with MetS were more likely to develop complications at both 30 and 90 days, including urinary incontinence, irritative voiding symptoms, and bleeding ( P < 0.001). After adjusting for potential confounders, patients with MetS had a greater than three times odds of both 30‐ and 90‐day complications compared to patients without MetS (30‐day adjusted odds ratio [aOR] 3.32, 95% confidence interval [CI] 2.21–5.01, P < 0.001; and 90‐day aOR 3.64, 95% CI 2.49–5.31, P < 0.001). Conclusion Metabolic syndrome was associated with a three‐fold likelihood of 30‐ and 90‐day complications after HoLEP. This could be an important factor to consider in preoperative counselling and patient selection.