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Abstract Background: There remains an opportunity for new therapies to improve long-term outcomes for patients with low-tumor burden follicular lymphoma (FL). Mosunetuzumab is an off-the-shelf CD20xCD3 bispecific antibody, approved as an intravenous therapy for patients with relapsed/refractory FL after ≥2 lines of systemic therapy. Mosunetuzumab can be administered in the outpatient setting as a fixed-duration regimen. In an open-label, multicenter, Phase II study conducted mainly across US community sites (MorningSun; NCT05207670), mosunetuzumab administered subcutaneously (SC) induced high response rates with a manageable safety profile in patients with previously untreated low-tumor burden FL (Burke et al. ASH 2024). Here we present updated efficacy and safety data for mosunetuzumab SC in patients with previously untreated, low-tumor burden FL. Methods: Patients had untreated Grade 1 or 2 low-tumor burden FL per Groupe d'Etude des Lymphomes Folliculaires criteria, Ann Arbor stage III/IV disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2. Mosunetuzumab SC was administered with step-up dosing in Cycle 1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg), then 45mg on D1 of each 21-day cycle. Hospitalization was not mandatory. Patients with a complete metabolic response after 8 cycles could complete therapy and patients with a partial metabolic response or stable disease continued treatment for up to 17 cycles. The primary endpoint was progression-free survival (PFS) at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), duration of response (DOR), duration of complete response (DOCR), and safety. Exploratory analyses assessed pharmacodynamic changes in B-cell subsets. Here, we report interim data. Results: As of February 10, 2025 (clinical cut-off date), 101 patients were enrolled from US community (n=56) and academic (n=45) centers; 52 patients had completed treatment, 21 had discontinued (mainly due to adverse events [AEs; n=6] and progressive disease [n=5]), and 28 were ongoing on treatment. Median age was 65 years (range: 34–82). Most patients had an ECOG PS of 0 (81.2%) or 1 (18.8%) and 43 patients (42.6%) had extranodal involvement. Median duration of follow-up was 13.8 months (95% confidence interval [CI]: 11.5–16.9) and median number of cycles received was 10 (range: 3–17). The ORR was 98.0% (95% CI: 93.0–99.8) and the complete response rate was 89.1% (95% CI: 81.3–94.4). Median TTR was 2.8 months (range: 1.4–8.3). Landmark DOR and DOCR rates at 12 months were 91.8% (95% CI: 81.5–96.5) and 95.7% (95% CI: 82.6–99.0), respectively. The 12-month PFS and OS rates were 92.0% (95% CI: 83.8‒96.1) and 99.0% (95% CI: 93.2‒99.9), respectively. The most common AE was injection-site reaction (ISR, 81.2%; Grade 1, 74.3%; Grade 2, 5.9%; Grade 3, 1.0%). Grade 3/4 AEs were reported in 51.5% of patients; the most common (≥10%) events were cytopenias (36.6%) and infections (11.9%). Cytokine release syndrome (CRS) was reported in 48.5% of patients (Grade 1, 40.6%; Grade 2, 7.9%). Overall,infections occurred in 63.4% of patients (Grade 1, 7.9%; Grade 2, 42.6%; Grade 3, 11.9%; Grade 5, 1.0%) with the most common (≥10%) being upper respiratory tract infection (21.8%), COVID-19 (17.8%), sinusitis (13.9%), and pneumonia (11.9%). At the time of data cut-off, ISR, CRS, and infection AEs were resolved at rates of 98.2%, 100%, and 89.0%, respectively. Two patients had a Grade 5 AE (sepsis, n=1; unknown cause, n=1).No immune effector cell-associated neurotoxicity syndrome events were reported. B-cell depletion was observed following the first dose of mosunetuzumab, with subsequent B-cell recovery observed within six months of treatment completion. Conclusions: Fixed-duration mosunetuzumab SC demonstrates high efficacy rates with deep and sustained responses in patients with previously untreated, low-tumor burden FL. The manageable safety profile supports ease of outpatient administration without mandatory hospitalization, including in community oncology practices. Additionally, exploratory analyses demonstrating B-cell recovery after treatment completion also substantiate the use of mosunetuzumab SC as a fixed-duration regimen. These data support further evaluation of mosunetuzumab SC in patients with previously untreated, low-tumor burden FL.

Abstract INTRODUCTION Outcomes for 1st relapse of pediatric B-lymphoblastic leukemia (B-ALL), especially high/intermediate-risk (HR/IR) relapse, remain unacceptably poor. Limited enrollment of this population on cooperative group clinical trials has impeded our ability to study potentially effective regimens. In the current era, patients can access innovative immunotherapies commercially. However, there is no mechanism to capture outcomes for these off-study patients and no comparative effectiveness data to guide treatment selection. METHODS We conducted a multicenter, retrospective study of patients <30 years who initiated 1st relapse therapy at a participating center from 2018-2022 (ReCALL-1 Study). Objectives were to define real-world survival outcomes, compare response rates of reinduction strategies, describe the post-reinduction treatment landscape, and, for patients with HR/IR relapse, assess the comparative effectiveness (CE) of blinatumomab to hematopoietic cell transplant (blina/HCT) v CD19 CAR T cells (CART). For the CE analysis, we emulated an open-label, randomized study of blina/HCT v CART who achieved an M1/M2 marrow at the end of an intensive reinduction (EoRI). Patients were classified by their intended treatment at EoRI. Cox regression models were used to adjust for unbalanced patient and disease features by arms. The primary outcome was overall survival (OS) from EoRI. RESULTS The full cohort included 479 patients from 33 centers (31 US, 2 international). Median time to relapse was 31 months (m); 77% had bone marrow (BM) involvement and 31% central nervous sytem involvement. With a median follow-up of 49m from relapse, 4 year (y) OS, event-free survival (EFS), and non-relapse mortality (NRM) were 64%, 43%, and 13%, respectively. Among patients with very early BM (<18m, n=79), early BM (18-35m, n=76), late BM (≥36m, n=162), and isolated CNS (n=85) relapses, 4y OS/EFS were 29%/20%, 57%/35%, 78%/49%, and 84%/61%, respectively. Only 19% received reinduction therapy on a clinical trial. Among patients with BM disease, R3 reinduction (n=179) and VXLD (n=61) had identical MRD-negative (<0.01%) CR rates of 38% (p=1.00) and equivalent treatment failure (TF; M3 or extramedullary disease) rates: R3, 8% v VXLD 7%, p=0.79. Blina (n=33) and inotuzumab-based (n=21) reinductions achieved MRD-negative CR rates of 39% and 52%, respectively, but higher TF rates of 39% and 24%. Reinduction mortality was 2%: R3, n=5; VXLD, n=3; 3-drug reinduction, n=1. Overall, as part of 1st relapse therapy, 36% received CART (78% commercial product), 44% HCT, 40% blina, and 11% inotuzumab. The emulated trial included 159 patients, 95 on blina/HCT and 64 on CART. Study arms were well matched by demographics, cytogenetics, and relapse sites, but CART patients were more likely to have relapsed <18m from diagnosis (34% v 24%) and have EoRI M2 marrows (31% v 11%), and less likely to have private insurance (36% v 51%). Unadjusted OS was comparable between arms (log rank p=0.18): CART, 60% at 4y; blina/HCT, 71%, as was NRM (10% v 13% at 4y). EFS was lower for CART (p=0.049): 4y EFS 35% v 49% for blina/HCT. After adjustment for unbalanced covariates, the hazard of death was equivalent for CART as compared to blina/HCT (aHR 1.1, 95% CI 0.6-2.1, p=0.67) and EFS became more comparable (aHR 1.3, 95% CI 0.8-2.1, p=0.22). 91% of blina/HCT and 97% of CART received their intended cell therapy; time from EoRI to cell therapy was shorter for CART (67 v 86 days, p<.001). In the CART arm, 34% underwent consolidative HCT; 1/3 were preplanned and 2/3 due to loss of B cell aplasia or NGS-MRD positivity. Of those with a 2nd relapse, CART patients were more likely to be CD19 negative (47% v 10%, p=0.003). CONCLUSION In this multicenter, real-world cohort of children treated for 1st relapse in the immunotherapy era, suboptimal outcomes for early BM relapse persisted, with particularly dismal 4y OS of 29% for relapses <18m after diagnosis. In contrast, survival for late BM and isolated CNS relapses compared favorably to historic data. Only 1 in 5 patients initiated relapse therapy on a clinical trial and although 1st relapse is not an approved indication for commercial CART in pediatrics, 36% received CART. In an emulated trial of post-reinduction blina/HCT v CART, adjusted EFS and OS were comparable, suggesting that CART may be a viable alternative to HCT for select patients. Post hoc analyses will identify whether specific subgroups may benefit more from one strategy.

Introduction Registrational trials are clinical trials which are used to justify regulatory approval of a new medication by the FDA. However, clinical trials may not be designed around patient-centred outcomes, like overall survival (OS) or quality of life. This disconnect raises concerns about whether current trial designs are truly aligned with the long-term needs and priorities of patients. A comprehensive analysis of trial designs and endpoints is necessary to ensure that future oncological therapies deliver meaningful clinical improvements. Our objective was to describe types of clinical trial design and primary endpoints used for registrational trials, and their trends over time. Research design and methods In this cohort study, the HemOnc database was used to identify registrational trials supporting cancer drug approval from 2004 through 2023. Clinical trial design (escalation, de-escalation, in-class switch, out-of-class switch) and primary endpoint (OS; time-to-event including progression-free survival; response-based endpoint) were characterized. Results Escalation trial designs were more common than in-class switches or out-of-class switches. De-escalation and mixed designs were exceedingly rare. The most common primary endpoint was a composite time-to-event endpoint. Conclusion Most clinical trials leading to FDA approval for cancer-directed therapies employ escalation designs with composite time-to-event endpoints. Designs reflecting paradigm shifts in therapy (in-class switches and out-of-class switches) are sparsely used. This approach raises the concern that trials may increase therapeutic toxicity without delivering meaningful improvements in OS or quality of life.

Abstract Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of cancer. However, the durable response to this therapy remains low, and there is a risk of moderate-to-severe toxicities following treatment that requires close monitoring. Over the past decade, we have learned that cytokines play an important role in mediating CAR T cell–associated toxicities and efficacy. As such, cytokine modulation has become a popular area of investigation to improve therapeutic responses. Although the relationship of many cytokines with CAR T-cell therapy has been investigated, several recent studies suggest paradoxical roles for cytokines such as IFNγ, IL2, IL4, and IL10 in CAR T-cell response and toxicity. In this review, we summarize the history of these cytokines in immunotherapies, detail the contexts in which these cytokines have been beneficial or harmful in the context of CAR T-cell therapy, and discuss factors that may be dictating their pleiotropy.

Objective To estimate the proportion of female patients from Mayo Clinic Family Medicine and Community Internal Medicine clinics who are aware of alcohol use as a breast cancer (BC) risk factor. Patients and Methods One thousand women aged 21 to 70 completed a survey collecting information on demographics, medical/family history, frequency and quantity of alcohol consumption, and other health behaviors. Participants were also asked to grade how likely certain factors were to increase lifetime BC risk. Results Most participants (844/990 [85.3%]) identified a family history of BC as a BC risk factor. In contrast, 48.4% (475/982) identified alcohol use as a BC risk factor. The remaining 51.6% (507/982) reported either they were not sure about alcohol consumption as a risk factor (341/982 [34.7%]), believed that there was no association (143/982 [14.6%]), or believed that alcohol consumption decreases the risk of BC (23/982 [2.3%]). In multivariable analyses, factors associated with awareness of alcohol consumption and BC risk included having never been pregnant ( P = 0.048), more education ( P < 0.001), and higher frequency of alcohol consumption in the past 12 months ( P = 0.005). Conclusion Further education of patients and the public is needed to promote awareness of alcohol as a risk factor for BC.

Abstract Objectives The primary objective of this research is to assess the content coverage of nursing data within a publicly available common data model (CDM), focusing on how nursing data, documented in flowsheets, are represented within the model. Materials and Methods This mapping study was informed by previous evaluation studies and serves as a framework for evaluating information resources, including to guide development and implementation. The overall research process consists of 4 steps: (1) identify a CDM; (2) define evaluation criteria; (3) map nursing flowsheet data; and (4) apply evaluation criteria. Results Overall, 65.5% (n = 1170) of the flowsheet concepts were mapped to Systematized Nomenclature of Medicine—Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC) target codes and 56.0% (n = 1831) of the flowsheet values were mapped to SNOMED CT and LOINC target codes. The flowsheet concepts had a higher average mapping time per concept/reviewer (1.19 min) as compared to the average mapping time per value/reviewer (0.64 min). Discussion This mapping study demonstrated the progress and ongoing challenges of mapping nursing data to a national common data model. However, the ability to use nursing data at scale in a national CDM remains limited until more comprehensive mapping is completed. Conclusion This mapping study identifies a significant gap in integrating nursing data into a national common data model, highlighting an opportunity to enhance patient care through improved real-time insights and evidence-based nursing practices. Addressing this gap can help shape policies that prioritize the inclusion of nursing data. Additionally, aligning nursing data at scale can advance research, increase efficiency, and optimize nurse-sensitive patient outcomes.

Abstract Objectives Society guidelines discourage biopsy of thymic epithelial tumours (TETs) due to the perceived risk of local seeding or pleural dissemination. However, few studies have evaluated this concern, and the true risk of preoperative biopsy remains unknown. Methods We queried the United States’ National Cancer Database for adults with localized TETs who underwent upfront R0 thymectomy 2004-2015. Use of preoperative biopsy over time was assessed with the Cochran-Armitage test. Postoperative outcomes were compared with chi-square and Wilcoxon rank sum tests. Overall survival (OS) was analysed with Kaplan-Meier and Cox proportional hazard methods. Results We identified 1056 patients. The median age was 61 years; 47% (492) were male. Use of preoperative percutaneous biopsy increased 2006-2015 from 18% to 33% (P &lt; .001). Patients who underwent biopsy had larger tumours [median 6.6 vs 5.0 cm], more open operations [72% (150) vs 62% (331)] and regional lymphadenectomies [44% (118) vs 33% (250)], and a longer length of hospitalization (median 4 vs 3 days). Thirty-day mortality was similar between the groups. There was no difference in 10-year OS between the biopsy and no-biopsy groups [75% (95% CI 69%-82%) vs 76% (95% CI 73%-80%), P = .8]. After adjusting for age, sex, primary payor, histology, and tumour size, OS was similar between the biopsy and no-biopsy groups [AHR 0.97 (95% CI 0.72-1.29), P = .9]. Conclusions In this analysis of patients with localized TETs undergoing upfront R0 thymectomy, preoperative biopsy is not associated with worse OS. More study is needed to further explore whether biopsy increases risk of recurrence.

Purpose: Despite the 2022 American Heart Association/American College of Cardiology guidelines recommending cardiac rehabilitation (CR) after aortic dissection repair, both patient participation in CR and the associated clinical outcomes remain poorly understood. Methods: Adults (≥18 years of age) discharged alive following thoracic aortic dissection surgery across the Mayo Clinic Enterprise (January 2012 to November 2022), with follow-up until May 2024, were included (IRB #24-001141). Data were presented using summary statistics and logistic regression modeling. Results: A total of 186 patients were referred; 37% were female, and the median age was 64 (51, 73) years. Dissections were classified as type A (43%), type B (18%), or a combination, and 55% had residual dissection. Over half (53%) did not start CR, with older age (aOR = 0.97: 95% CI, 0.94 - 0.99; P = .003), family history of aortic dissections and/or aneurysms (aOR = 0.17: 95% CI, 0.04 - 0.54; P = .005), and tobacco use (aOR = 0.35: 95% CI, 0.13 - 0.91; P = .037) being associated with lower odds of enrollment. Of the 87 who enrolled, 34 did so at a Mayo Clinic facility. There were no complications, with no difference in adverse outcomes. Among those with evaluations at graduation from CR (n = 21), quality of life (Dartmouth index 16 [14, 19] vs 25 [22, 30]; P = .002) and 6-minute walk distance (488 [375, 531] vs 302 [235, 398] m; P = .001) improved. Conclusions: Following thoracic aortic dissection repair, CR significantly improved quality of life and functional capacity without adverse events. Further work is needed to improve enrollment and establish data-driven safety margins for exercise.

Objectives: To determine the risk of developing de novo carpal tunnel syndrome (CTS), arthritis, or rheumatoid arthritis in women who underwent hysterectomy with bilateral ovarian conservation (H-OC) before reaching spontaneous menopause. Methods: We identified 1,573 women undergoing H-OC for a benign indication at age 18 to 44 years between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman who had not undergone hysterectomy or oophorectomy before the matching date (index date). Diagnostic codes for CTS and arthritis were extracted from the Rochester Epidemiology Project medical records-linkage system through 2019. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models and the two cohorts were balanced for 19 chronic conditions and for several potential confounders present at index date. Results: Over a median 25.8-year follow-up, women undergoing H-OC had an increased risk of developing CTS (HR: 1.33; 95% CI: 1.13-1.56) compared with referent women. The risk was similar in strata by age at H-OC and was higher for women with endometriosis and menstrual disorders indications. Women undergoing H-OC also had an increased risk of developing arthritis (HR: 1.34; 95% CI: 1.23-1.47). The risk was similar in strata by age at H-OC and by indication. Rheumatoid arthritis considered separately was also associated with H-OC (HR: 1.55; 95% CI: 1.05-2.30). Conclusions: H-OC was associated with an increased risk of de novo CTS, arthritis (all types), and rheumatoid arthritis. Further studies are needed to confirm these associations and to explore potential biological mechanisms.