Citations

Abstract The Bridging the Gaps (BTG) in Leukemia, Lymphoma and Multiple Myeloma Consensus Conference 2025 brought together a multidisciplinary group of oncology experts to address the complexities of lymphoma management, focusing on mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and diffuse large B‐cell lymphoma (DLBCL). This article presents consensus recommendations developed through a modified Delphi process, which emphasize the need for tailored therapeutic strategies in light of recent advancements in treatment options. Key recommendations include the screening for high‐risk features in MCL, use of the BOVen regimen (zanubrutinib, obinutuzumab, and venetoclax) for TP53 ‐aberrant cases, and integration of chimeric antigen receptor T‐cell therapy for patients with mantle cell lymphoma that is refractory to covalent Bruton tyrosine kinase inhibitors. For CLL, recommendations include consideration of time‐limited therapies for younger patients and a “watch and wait” strategy for asymptomatic patients despite the improved activity and safety of current treatment regimens. For DLBCL, this article highlights the challenges in treatment sequencing and the role of circulating tumor DNA and minimal residual disease testing in monitoring disease progression. Overall, the conference describes the importance of ongoing research to refine management strategies and improve patient outcomes in lymphoma care, addressing the gaps in clinical practice where high‐level evidence is lacking.

PURPOSE Approximately three quarters of patients with sarcoma report financial toxicity, defined as the psychosocial and economic burden of cancer care. The Comprehensive Score for Financial Toxicity (COST) is a screening questionnaire validated in patients with cancer. However, its use is not widespread in sarcoma care, likely in part due to its complexity. This study aimed to characterize financial toxicity in patients with sarcoma and evaluate whether shorter screening tools can identify high-risk patients. METHODS We conducted a survey and retrospective cohort study of patients treated for sarcoma at a large, academic sarcoma center in 2016-2024. Patients completed the COST questionnaire (11 graded questions, each scored on a five-point Likert scale from 0 to 4) and the shorter, four-question Worry about Affording Healthcare Scale (WAHS). We obtained clinical information from the electronic health record. We used descriptive statistics to summarize responses to COST, Pearson's correlation coefficient to assess the association between WAHS and COST, and stepwise Spearman correlations to evaluate whether an abbreviated (1-4 question) version of COST correlated highly with total COST score. RESULTS Among 205 participants, the mean COST score was 20/44 (standard deviation = 6; lower scores indicate greater financial toxicity). Respondents worried most about job loss (mean COST: 0.99) and family finances (mean COST: 1.11). WAHS was weakly correlated with COST (r = 0.47, P < .01). A four-item abbreviated COST tool was strongly correlated with the total COST (ρ = 0.906, P < .0001) and demonstrated high sensitivity (96%) and moderate specificity (75%). CONCLUSION An abbreviated four-item COST tool could act as a clinically feasible, accurate screening tool after external validation. Routine financial toxicity screening could facilitate timely detection and referral to essential financial navigation resources.

Introduction Preoperative testosterone exposure has been associated with various health outcomes, but its impact on postoperative complications in patients undergoing total shoulder arthroplasty (TSA) has not been fully explored. This study aims to evaluate the association between preoperative testosterone exposure and postoperative medical and surgical complications in patients undergoing TSA. Methods A retrospective cohort study was conducted using the PearlDiver database. Patients who underwent TSA and used preoperative testosterone within 3 months of the index procedure were identified and matched 1:4 to controls without testosterone use using propensity score matching. Matching was performed based on age, gender, comorbidities, Charlson comorbidity index, obesity, tobacco use, and hypogonadism to balance the groups. Postoperative complications were assessed at 90 days and five years. Statistical comparisons were made using odds ratios (ORs) with 95% confidence intervals (CIs), and a p -value of <0.05 was considered statistically significant. Results The matched cohort included 677 testosterone users and 2554 controls. There were no statistically significant differences between the testosterone and control groups in 90-day complications such as myocardial infarction (OR 2.52, P = 0.31), pneumonia (OR 0.86, P = 0.70), and deep vein thrombosis (no cases in the testosterone group). Over five years, the testosterone group had a significantly higher risk of periprosthetic joint infection (4.1% vs. 2.4%, OR 1.76, 95% CI 1.10–2.75, P = 0.015), but no differences in revision rates, dislocation, aseptic loosening, or stiffness were observed. Conclusion Preoperative testosterone exposure was associated with a higher risk of periprosthetic joint infection following TSA, but no significant differences were found in major medical complications or revision rates.

Abstract Background: Patients with residual invasive disease after neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer remain at high risk for recurrence even with standard adjuvant trastuzumab emtansine (T-DM1). H2NVAC, a multi-epitope HER2 peptide vaccine, has previously demonstrated the ability to elicit robust and durable immune responses. Here, we assessed the safety and early immunogenicity of H2NVAC in combination with T-DM1 in this high-risk population. Methods: Patients with stage II-III HER2-positive breast cancer and residual invasive disease following NAC and HER2-directed therapy received standard adjuvant T-DM1 alongside six priming doses of H2NVAC administered every 3 weeks. The primary endpoint was the occurrence of dose-limiting toxicity (DLT) within 21 days of the first vaccination, with adverse events graded per CTCAE v5.0. Immunogenicity assessments included HER2-specific T-cell responses measured by IFNγ ELISpot and HER-specific serum antibodies measured by ELISA at baseline and 30 days after the sixth priming dose. Results: 20 patients were enrolled. H2NVAC plus T-DM1 was well tolerated with no DLTs observed. All treatment-emergent AEs were grade 1-2, with fatigue (grade 1 60%, grade 2 5%), peripheral sensory neuropathy (grade 1 35%, grade 2 10%), elevated alkaline phosphatase (grade 1 40%), nausea (grade 1 35%, grade 2 5%), arthralgia (grade 1 30%), and injection-site reactions (grade 1 50%) being most common. Robust vaccine-specific T-cell responses by ELISpot were observed in 94% of evaluable patients, who mounted HER2-specific T-cell responses at 30 days after the sixth priming dose, with a mean 197-fold increase over baseline. Further CYTOF analysis showed a significant decrease in exhausted T-cell phenotypes, with reduced LAG3 and TIM3 expression on both CD4+ and CD8+ T cells. For antibody responses by ELISA, 26% of patients developed HER2 protein-specific antibody responses at this time point. There was no significant increase in antibodies to H2NVAC peptides or to unrelated tumor antigens (p53, IGFBP2, TERT, myoglobin) at 30 days after the sixth vaccine. Ongoing correlative analyses will assess the evolution of immune responses at later time points following completion of T-DM1 therapy. Conclusions: Concurrent administration of H2NVAC with T-DM1 was safe and did not increase toxicity beyond single-agent T-DM1. To our knowledge, this is the first study to demonstrate that a cancer vaccine can be delivered concurrently with an antibody-drug conjugate without increasing adverse effects while still eliciting robust T-cell responses. Ongoing analyses will further define the kinetics and durability of vaccine-induced antibody and T-cell responses at later time points, as well as evaluate the efficacy of H2NVAC in reducing recurrence risk in the randomized phase 2 trial. Citation Format: Saranya Chumsri, Sharmila Giri, Andy J. Ness, David W. Hillman, Nadine Norton, Davitte Cogen, Brian M. Necela, Aziza Nassar, Donald W. Northfelt, Pooja Advani, Rohit Rao, Alvaro Mareno-Aspitia, Brenda Ernst, Kathryn J. Ruddy, Matthew P. Goetz, Keith L. Knutson. Safety, tolerability, and early immune responses in the safety run-in of an HER2 multi-epitope vaccine combined with T-DM1 in residual HER2-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6715.

Abstract Background: Epidemiologic and other studies have identified environmental, occupational, and genetic risk factors for lymphoid and myeloid malignancies, but most studies have been conducted in Western populations. Investigations in populations with differing exposure patterns, distributions of disease subtypes, and genetic architecture are needed to fully understand hematopoietic tumor etiology. Methods: We conducted a large, multicenter, hospital-based case-control study of lymphoid and myeloid neoplasms in East Asia (AsiaLymph), including 5,671 lymphoid cases, 1,879 myeloid cases, and 3,858 controls. Participants completed a computer-assisted personal interview and provided biospecimens. Cases underwent central pathology review and were coded into the WHO Classification. Herein, we describe the study methods in detail and report association results for education, body mass index, and family history. Results: Greater BMI at age 20 but not at age 40 was associated with odds of total lymphoid neoplasm (per 5 kg/m2 increase: OR [95% CI]: 1.18 [1.09-1.27]), total myeloid neoplasm (OR [95% CI]: 1.17 [1.05-1.29]), and several subtypes. Greater educational attainment was associated with increased odds of total lymphoid neoplasm (for college vs. less than primary education: OR [95% CI]: 1.41 [1.21-1.65]) but not myeloid neoplasm (OR [95% CI]: 1.17 [0.95-1.45]; p-heterogeneity=0.02). There were also positive associations between family history of hematologic cancer in first degree relatives and odds of lymphoid neoplasm (OR [95% CI]: 1.53 [1.15-2.03]) and myeloid neoplasm (OR [95% CI]: 1.65 [1.11-2.44]) and specific subtypes. None of the evaluated risk factors were associated with NK/T-cell lymphoma, which supports a distinct etiology for this subtype. Conclusion: The AsiaLymph Study is one of the largest molecular epidemiology studies of both lymphoid and myeloid neoplasms with standardized World Health Organization classification of histopathologic subtypes and will serve as a valuable resource for etiologic investigations into risk factors for these malignancies. Citation Format: Qing Lan, Lauren M. Hurwitz, John K. Chan, Tai Hing Lam, Kexin Chen, Yok Lam Kwong, Xu Caigang, Brian CH Chiu, Raymond Liang, Ip Dennis, Wei Hu, Bryan Bassig, Mark Purdue, Jun Xu, Sarah Locke, Sophia S. Wang, James R. Cerhan, Sonja Berndt, Jonathan N. Hofmann, Jianxin Shi, Kai Yu, Shahinaz Gadalla, Lisa J. McReynolds, Rena Jones, Hongji Dai, Zhangyan Lyu, Lugui Qiu, Wei Liu, Huilai Zhang, Xianhuo Wang, Lindsay M. Morton, Stephen Chanock, Martha Linet, Melissa C. Friesen, Roel Vermeulen, Nathaniel Rothman. A multi-center hospital-based case-control study of lymphoid and myeloid neoplasms (AsiaLymph): Study design and initial findings for education, body mass index, and family history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5051.

Abstract Introduction: The National Cancer Institute estimated almost 317,000 new breast cancer and over 13,000 new cervical cancer cases in 2025. While the National Breast and Cervical Cancer Early Detection Program has served millions of women over the past two decades, inequities in cancer screening, subsequently delayed diagnosis, and timely and appropriate treatment remain a public health challenge in the United States. Despite the substantial impact of social determinants of health (SDOH) on cancer screening, few studies have accounted for SDOH at the individual level when assessing breast and cervical cancer screening adherence. The primary objective of this study is to examine whether the individual-level SDOH, measured using HOUsing-based SocioEconomic Status (HOUSES) index, is associated with breast and cervical cancer screening non-adherence (not current on respective USPSTF recommendations for age and frequency). Methods: In this retrospective study, patients were identified as those receiving primary care in the Mayo Clinic Health System and Mayo Clinic (Rochester, MN). The Midwest Quality Metrics panel was then used to assess patients due for screening for breast or cervical cancer in July 2023. The HOUSES, using home address and publicly available data on the residence which measures and categorizes housing status into quartiles, was obtained using the electronic health records (EHRs)-linkable patient-level information. Logistic regression analyses were conducted, controlling for Census block group-level adverse social exposome from the Area Deprivation Index, age, and comorbidities. Results are presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: For breast cancer, among 128,462 eligible patients, 20.1% (n= 25,857) were non-adherent. Compared to the highest HOUSES quartile (Q4), lower HOUSES groups showed significantly higher odds of non-adherence: Q3 OR=1.20 (95% CI=1.15, 1.25), Q2 OR=1.45; (95% CI=1.40, 1.53), and Q1 OR=1.90 (95% CI=1.81, 1.99). For cervical cancer, among 175,712 eligible patients, 29.9% (n=52,533) were non-adherent. Compared to the highest HOUSES quartile (Q4), lower HOUSES groups showed significantly higher odds of non-adherence: Q3 OR=1.07 (95% CI=1.03, 1.10), Q2 OR=1.16; (95% CI=1.12, 1.20), and Q1 OR=1.36 (95% CI=1.31, 1.41). Conclusions: A clinically meaningful association between the HOUSES index and cancer screening adherence was observed. A lower HOUSES index was associated with higher odds of non-adherence for both breast and cervical cancer screening, even after accounting for neighborhood-level risk, age, and comorbidities. Incorporating HOUSES into EHRs can be a practical “screening-for-screening” tool that enables close monitoring of higher-risk patients without additional burden of surveys. Citation Format: Eunice Y. Park, Madison Beenken, Dave Watson, Chung Il Wi, Tufia Haddad, Gladys Asiedu, Karla BALLMAN, James R. Cerhan, Carolyn Flock, Brian Lynch, Folakemi T. Odedina, Scott H. Okuno, Young J Juhn, . HOUSES as a screening tool for cancer screening: Patient-level housing-based socioeconomic status and breast and cervical cancer screening adherence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7599.

Abstract Background: The cellular balance between saturated and monounsaturated fatty acids is a defining feature of tumor lipid metabolism, with SCD1 functioning as a key modulator through the production of MUFAs. Elevated SCD1 activity and MUFA accumulation have been documented in hepatocellular carcinomas, although the consequences of restricting MUFA synthesis have not been fully clarified. Methods: A selective SCD1 inhibitor, SSI-4, was evaluated across established human HCC cell lines and xenograft models. Measurements included cell viability, lipid compositional analyses, and characterization of stress response pathways at both molecular and biochemical levels. The effects of MUFA depletion were studied in vitro and in vivo, with attention to ER stress, apoptosis, ferroptosis markers, and autophagy induction. Results: SSI-4 treatment led to marked reduction in cellular MUFA content and an increase in saturated fatty acid pools. The resulting metabolic stress correlated with activation of unfolded protein response components, caspase-mediated cell death, and the upregulation of ferroptosis-associated genes. Triglyceride and MUFA levels declined precipitously, as confirmed by mass spectrometry-based lipidomics. Tumor growth was suppressed in PDX models and evidence of autophagic flux was apparent in sensitive cell lines. Variability in response highlights metabolic heterogeneity in HCC. Conclusions: Targeted disruption of MUFA biosynthesis inflicts metabolic vulnerability on HCC cells, precipitating membrane alterations and activation of multiple cell death programs. These findings recommend further investigation into metabolic interventions exploiting MUFA depletion, with consideration for stratifying patients according to lipid metabolic phenotypes. Funding: This work is supported by Mayo Clinic Comprehensive Cancer Center and the Jay and Deanie Stein Career Development Award for Cancer Research at Mayo Clinic Jacksonville and the Mayo Clinic Translational Hepatobiliary Cancer SPORE P50CA210964 Career Enhancement Program (CEP) and Florida Department of Health/Florida Cancer Innovation Fund C25C23. Citation Format: Justyna J. Gleba, Victoria N. Rios, Brian M. Necela, Skyeler M. Klinge, Matt L. Pawlush, Mike J. Redig, Aylin Alasonyalilar-Demirer, Han W. Tun, John A. Copland III, . Disrupting tumor lipid homeostasis by MUFA depletion drives cell death in HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7333.