Citations

e13635 Background: Melanoma is an aggressive skin malignancy with rising global incidence, for which checkpoint inhibitors (CPI) and BRAF-targeted therapies are standard of care in advanced disease. However, access to molecular diagnostics and CPI remains limited in conflict-affected regions such as Syria. Real-world data describing melanoma management in this setting are scarce. Methods: We conducted a retrospective study of all patients diagnosed with melanoma between 2022 and 2024 at Al-Bairouni University Hospital (ABUH), Syria’s primary oncology referral center. Demographic and clinical characteristics were analyzed for the entire cohort, and patients with advanced disease were evaluated for molecular testing and treatment patterns. Semi-structured interviews were conducted in a mixed advanced cancer subset (N = 35) to explore barriers to immunotherapy access. Results: Among 115 patients with melanoma, the median age at diagnosis was 57 years (IQR 44.5–67), and 54.7% were male. At presentation, 18.3% had stage I disease, 1.7% stage II, 2.6% stage III, and 40.9% stage IV disease; staging was unavailable in 36.5%. Among patients with advanced melanoma (n = 47), BRAF testing was performed in 17 (36.2%), with targeted therapy administered to 5/16 BRAF-positive patients. Only 7/47 patients (14.9%) received CPI, primarily as monotherapy. In the qualitative subset (predominantly lung cancer), five major barriers to immunotherapy access emerged: financial toxicity (n = 22), limited drug availability (n = 9), limited patient awareness (n = 8), geographic/logistical challenges (n = 5), and system delays (n = 4). Conclusions: Despite a substantial burden of advanced melanoma, access to molecular testing, targeted therapy and CPI in Syria remains limited. Qualitative findings highlight financial and structural barriers as primary drivers of limited access, underscoring the need for improved drug availability, diagnostic infrastructure, and patient education in conflict-affected settings.

8094 Background: Patients with extensive-stage small cell lung cancer (ES-SCLC) who progress after platinum-based chemotherapy plus immunotherapy have limited options. Whether adding lurbinectedin while continuing immune checkpoint blockade at relapse improves outcomes is unknown. We report results for the platinum-resistant cohort (progression ≤3 months from last chemotherapy) of MC1923. Methods: MC1923 is a phase II trial using a Simon optimal two-stage design. Patients were assigned to a starting dose of durvalumab 1500 mg IV plus lurbinectedin 3.2 mg/m 2 IV on Day 1 of 21-day cycle. The primary endpoint was the 6-month progression-free survival rate (PFS6). Accrual continued to 22 eligible patients if ≥2/9 achieved PFS6; the regimen would be considered promising if ≥7/22 (32%) were alive and progression-free at 6 months. Secondary endpoints included adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-two patients enrolled (02/04/2022–05/21/2025); all were eligible and treated. Median age was 66 years; 32% were male; ECOG performance status was 0 in 9% and 1 in 91%; 96% had prior atezolizumab. Median cycles delivered were 4 (range 1–13). PFS6 was 4/22 (18.2%; 95% CI, 7.5–44.1%), below the prespecified threshold. Median PFS was 3.1 months (95% CI, 1.6–5.3). ORR was 13.6% (3/22; all partial responses; 95% CI, 2.9–34.9%). At data cutoff (12/18/2025), 4 patients were alive; median follow-up was 16.8 months (range 5.5–39.6). Median OS was 7.4 months (95% CI, 4.3–18.6) and 1-year OS was 33.1% (95% CI, 17.6–61.9%). One (1) patient discontinued treatment with durvalumab due to AE. No treatment-related Grade 5 AEs occurred; Grade 3–4 AEs at least possibly related to treatment occurred in 32% (7/22); Grade 4 AEs occurred in 5% (1/22), all hematologic. Most common Grade 3 AEs were decreased neutrophils and white blood cells (each 9%). Conclusions: Durvalumab plus lurbinectedin demonstrated manageable toxicity in platinum-resistant ES-SCLC after chemoimmunotherapy but did not meet the prespecified PFS6 efficacy threshold, supporting the need for alternative strategies in this high-risk population. Clinical trial information: NCT04607954 .

7533 Background: Ciltacabtagene autoleucel (cilta-cel) shows benefit for patients (pts) with relapsed/refractory multiple myeloma (RRMM). A recently recognized uncommon adverse reaction, IEC-EC is characterized by severe/persistent diarrhea typically 1–3 months post CAR-T cell infusion. Here we summarize incidence and features of IEC-EC in clinical trials of cilta-cel for RRMM. Methods: 483 pts across RRMM studies (CARTITUDE-1, -2, -4, and CARTIFAN-1) were evaluated for evidence of IEC-EC. The clinical picture and nomenclature for IEC-EC were described in the real-world setting after infusion of most pts. As such, retrospective analysis was performed to identify cases consistent with IEC-EC, defined as prolonged (≥3 weeks) and severe (≥grade 3) diarrhea after cilta-cel infusion, without clear infectious etiology. Correlative biomarker analyses included peripheral CAR-T cell expansion/persistence, immune cell composition, and cytokines/inflammatory markers. Centralized pathomorphological review and immunohistochemical analysis of available biopsies was conducted. Results: Across RRMM studies, 6/483 (1.2%) pts demonstrated the clinical picture of IEC-EC, presenting 12–214 days after receiving cilta-cel (median onset 67 days post infusion). Best response was CR/sCR for all subjects. Pts received therapies including steroids (4/6). Four pts experienced symptom resolution within 123–227 days; 2 had persistent symptoms until death (causes: multiorgan failure and COVID19). Pts with IEC-EC had lower levels of B cells and higher levels of CAR+ T cells and inflammatory cytokines (eg, IL-6) at onset compared to a GI symptom-free control group at comparable time; while all cilta-cel–treated pts experienced B cell depletion, pts with IEC-EC had more prolonged deficiency. Histological analyses of GI biopsies from 5 pts with IEC-EC revealed plasma cells, normally present in the GI tract, were absent. CAR-T cells were detected and localized to the lamina propria and were not observed juxtaposed with epithelia, making it unlikely direct damage to epithelia was caused by CAR-T cells. Histologic damage was greater in the small intestine (predominantly duodenum) than the colon. Conclusions: Retrospective analysis of cilta-cel trials identified a low IEC-EC incidence (1.2%). Findings support a reactive mechanism involving plasma cell depletion and immune dysregulation rather than direct CAR-T cell cytotoxicity and highlight the importance of upper endoscopy to identify injury patterns in the small intestine that may be less pronounced in the colon. Although the pathophysiology is not fully defined, increased awareness and earlier diagnosis may improve understanding of management and enhance likelihood of IEC-EC reversibility.

3592 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent dose-limiting toxicity from oxaliplatin that impairs quality of life in gastrointestinal (GI) cancer patients (pts). While strategies to limit exposure exist, their impact on survival remains debated. We evaluated whether reduced oxaliplatin exposure (ROE) maintains survival while mitigating toxicity. Methods: We conducted a systematic review and meta-analysis (PubMed, Embase, Scopus, Web of Science, EBM Reviews) of studies comparing ROE vs standard-duration oxaliplatin-based chemotherapy in GI cancers. ROE was defined as planned limitation of oxaliplatin exposure, including shortened duration (3-4 months), maintenance-based de-escalation, or stop-and-go strategies. Primary endpoints were disease-free survival (DFS) in curative settings, progression-free survival (PFS) in palliative settings, and overall survival (OS). Secondary endpoints included grade ≥3 CIPN and grade ≥3 adverse events (AEs). Random-effects models used Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed via I² and Cochran’s Q. Results: 24 studies, comprising 15 randomized controlled trials (RCTs) and 9 retrospective cohorts, were included (N = 30,404 pts; ROE: 13,348; control: 17,056). Settings included adjuvant colorectal cancer (CRC; n = 14), metastatic CRC (mCRC; n = 5), gastric cancer (GC) (adjuvant n = 1, metastatic n = 3), and metastatic pancreatic cancer (PDAC) (n = 1). ROE strategies included shortened duration (n = 14), maintenance (n = 8), and stop-and-go (n = 2). In adjuvant CRC, ROE did not compromise DFS (HR 1.07; 95% CI, 0.98-1.16; p = 0.12; I² = 21.7%), including in high-risk subgroups (HR 1.14; 95% CI, 0.93-1.40; p = 0.14; I² = 38.9%); OS was also not different between groups (HR 1.00; 95% CI, 0.94-1.07; p = 0.89; I² = 0%), including high-risk pts (HR 1.01; 95% CI, 0.93-1.10; p = 0.68; I² = 0%). In mCRC, ROE showed no detriment to PFS (HR 1.11; 95% CI, 0.99-1.25; p = 0.07; I² = 0%) or OS (HR 1.06; 95% CI, 0.92-1.23; p = 0.33; I² = 0%). Similarly, in metastatic gastric cancer, PFS (HR 0.82; 95% CI, 0.34-1.99; p = 0.44; I² = 77.3%) and OS (HR 0.90; 95% CI, 0.67-1.21; p = 0.26; I² = 0%) were comparable. Findings remained concordant after restricting the analysis to only RCTs. Pooled analysis was not feasible for PDAC and adjuvant GC studies, but individual study findings were consistent with the above. ROE significantly reduced the risk of grade ≥3 CIPN (OR 0.32; 95% CI, 0.20-0.53; p < 0.001; I² = 80.6%) and overall grade ≥3 AEs (OR 0.65; 95% CI, 0.50-0.86; p = 0.01; I² = 59.9%). Conclusions: Across GI malignancies, ROE was not associated with inferior DFS, PFS, or OS and was associated with lower rates of severe neurotoxicity and high-grade AEs. These findings support planned limitation of oxaliplatin exposure as a strategy to improve the therapeutic index of oxaliplatin-based chemotherapy across disease settings.

11059 Background: Payments from the drug industry to oncologists are common and influence physicians’ prescribing decisions. However, whether payments affect the likelihood that patients receive optimal cancer treatment has not been assessed. Methods: This was a population-based cohort study. We used fee-for-service Medicare claims to identify patients with incident cancer diagnosis (new cancer diagnosis code after >= 1 year with no cancer diagnosis codes) from 2014-2020. We used National Comprehensive Cancer Network (NCCN) Guidelines to identify treatment scenarios (e.g., metastatic melanoma, stage III colon adjuvant therapy) with variation in the clinical benefit among recommended treatment options. The patient cohort corresponding to each scenario was identified using claims. We used NCCN Guidelines to identify the “optimal” treatment for each scenario (defined as the designated “preferred” treatment, with NCCN Evidence Blocks scores used for tiebreaks) at each time point across the study period. The primary outcome was whether a patient received the treatment that was, as of their diagnosis date, the optimal treatment for their cancer (vs. any non-optimal treatment). The primary exposure[s] were whether a patient’s medical oncologist received personal (“general”) payments (source: linked Open Payments data) related to 1) optimal treatment or 2) any non-optimal treatment, during the year prior to the patient’s cancer diagnosis. We fit Poisson-family generalized estimating equations, with physician-level clustering and adjustment for scenario, year, and patient characteristics, to estimate the relative risk (RR) of optimal treatment. Results: There were 14 clinical scenarios comprising 15,835 patients. There were 3,429 (21.7%) patients whose oncologist received payment for the optimal treatment, 4,891 (30.9%) for non-optimal payments, and 1,993 (12.6%) to both payment types. Oncologist receipt of payment for optimal treatment was associated with a greater likelihood (RR=1.07, 95%CI:1.01-1.13), and payment for non-optimal treatment was associated with lower likelihood (RR= 0.94, 95%CI:0.89-0.98) of patients receiving optimal treatment. Associations became stronger as payment dollar value increased; for optimal payments ≥$10,000, RR=1.26 (95%CI:1.02-1.57), and for non-optimal payments ≥$10,000, RR=0.70 (95%CI: 0.49-1.00). An estimated 41.6% of unexposed patients received optimal treatment; versus 52.6%, 29.3%, and 33.8% among patients exposed to ≥$10,000 of payments for optimal treatment only, ≥$10,000 non-optimal payments only, and ≥$10,000 of both payment types, respectively. Conclusions: Industry payments related to the optimal cancer treatment were associated with increased use of the optimal treatment. However, payments related to non-optimal treatments were more common and were associated with decreased use of optimal treatment.

Color Doppler twinkling improves visibility and ultrasound-guided localization of biopsy markers made of polymethyl methacrylate (PMMA). This study examines the time- and frequency-domain features of twinkling. We performed beamforming on the raw radiofrequency (RF) data collected using a L7-4 transducer, followed by in-phase/quadrature (IQ) demodulation and wall filtering. Frequency content variations were evaluated both within individual Doppler ensembles (pulse-to-pulse) and across multiple frames. Normalized FFT magnitude spectra were computed for both twinkling and non-twinkling (metal) cases using beamformed RF and IQ data. The median of the normalized FFT magnitude (3–10 MHz) was consistently higher for the twinkling case compared to the metal case across RF (–13.75 dB vs –17.29 dB) and the IQ real component (–12.72 dB vs –16.15 dB), indicating broader and more energetic spectral content in twinkling. The frequency spread above the –20 dB threshold was approximately 2.5 times wider (5.38 MHz vs 1.95 MHz) in the twinkling case compared to the metal case. In time domain, the RMS of the standard deviation for the twinkling signal was approximately 28 times higher than that of the metal case across both RF and IQ data. These findings indicate that the ultrasound data from twinkling exhibits a more distributed frequency profile, consistent with observed aperiodic nature.

Objective To comprehensively examine hypertension- and heart failure–related mortality rates in the United States to develop a targeted approach to health policy development. Methods We analyzed death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database, focusing on mortality caused by hypertensive heart failure in adults aged ≥25 years from 2006 to 2020. Age-adjusted mortality rates per 1,000,000 and annual percent changes were calculated and categorized by year, sex, race, urban status, age group, and census region. Results A total of 268,545 deaths occurred due to hypertensive heart failure between 2006 and 2020. The overall age-adjusted mortality rates increased from 60.5 in 2006 to 134.9 in 2020. Males had higher age-adjusted mortality rates than women (76.6 vs. 73.8). Older-aged people exhibited significantly higher age-adjusted mortality rates than young and middle-aged adults. Age-adjusted mortality rates were highest in non-Hispanic Blacks/African Americans and lowest in non-Hispanic Asians/Pacific Islanders (126.8–43.6). Furthermore, age-adjusted mortality rates were highest in individuals from nonmetropolitan areas and the Western region. Conclusion Following a period of decline, the age-adjusted mortality rates increased until 2020. The highest age-adjusted mortality rates were observed in non-Hispanic Blacks and nonmetropolitan areas. An urgent restructuring of healthcare policy is needed to reduce heart failure-associated mortality.

Abstract Background: Tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager (TCE) is FDA approved in patients (pts) with extensive stage small cell lung cancer (ES-SCLC), after progression on frontline chemoimmunotherapy. We aimed to evaluate the immune cell profile in pts who received this therapy in standard-of-care (SOC) practice with progression free survival (PFS) less than and greater than two months (mo). Methods: Patients who received tarlatamab at Mayo Clinic Rochester and consented to immuno phenotyping of blood are included in the present study. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Microsoft Excel and PRISM. Results: Eighteen patients with median age 64 (range 37-79) were included in the study. 66% of our cohort were women and 83% had present or past history of smoking, with an average of 40 pack years (range 26-60). With a median follow-up of 2 months, the median PFS for the cohort was 1.5 mo (range 0.33-2.76 months). 61% (13/18) of patients had PFS &lt;2mo. 39% (5/18) had PFS&gt;2mo and of which, three patients had partial response with one maintaining stable disease and one patient with mixed response. At baseline (BL), there were no difference in T cell, CD4 or CD8 cell count between patients in the PFS&lt;2mo and PFS&gt;2mo groups. Patients with PFS&lt;2mo had higher exhausted CD8 T cells compared to those in the PFS&gt;2mo group (CD8+PD1+TIGIT+CD57+, PFS&lt;3mo vs &gt;3mo, cells/mL: 7.14±4.28, 1.58±1.37, p=0.009). Additionally, when analyzing the B-cell population, the PFS&lt;2mo group had lower percentage of B cells compared to the group with PFS&gt;2mo at baseline (6.0±7.5, 10.4±14, p=0.02). At day 7, the group with PFS&lt;2mo had lower Treg compared to the group with PFS&gt;2mo (2.88±1.38, 4.60±1.47, p=0.02). Also, the PFS&lt;2mo group had an increase of B cells compared to the group with PFS&gt;2mo at day 7(&lt;2mo vs &gt;2mo: 10.0±14, 4.37±3.07, p=0.04). Finally, the group with PFS&gt;2mo had decrease in total monocytes (mono), classical mono, and immunosuppressive cells (PFS&lt;2mo vs &gt;2mo, Mono: 340±347, 253±106, p=0.04. Classical mono: 305±283, 155±109, p=0.02. CD14+HLA-DRneg: 105.8±96, 12±39, p=0.03) compared to the group with PFS&lt;2mo by day 7. While no changes were seen between BL and day 7 for intermediate mono in PFS&lt;2mo group, PFS&gt;2mo group had decreased post treatment intermediate monocytes (BL vs day 7, cells/mL, intermed mono: 32.5±15,17.7±6.2, p=0.03). Conclusion: In this study investigating the SOC outcomes of tarlatamab, early progression was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at AACR meeting. Citation Format: Dhauna Karam Prasad, Andre De Menezes Silva Corraes, Malvika Gupta, Audrey Ma, Chen Wu, Zuoyi Shao, Kevin Reagan, Rayaan Kamal, Ashley Potter, Abdullah Al-Ajmi, Syeda Mina, Sykler J. Taylor, Antonious Hazim, Anastasios Dimou, Kaushal Parikh, Mohammed Shanshal, Ailsa Luce, Anna Schwecke, Julian Molina, Aaron Mansfield, Katherine Smith, Lucy Holmes, Haidong Dong, Yi Lin, Konstantinos Leventakos. Immune cell profile changes in patients treated with tarlatamab for extensive stage small cell lung cancer in real world practice [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 3931.

ABSTRACT Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors improve glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). However, their impact on quality of life (QoL) and patient‐reported outcomes (PROs) has not been systematically evaluated. We conducted a systematic review and meta‐analysis to assess the effect of SGLT2 inhibitors on QoL in patients with T2DM. Methods MEDLINE, Embase, Scopus, Cochrane and ClinicalTrials.gov were searched until 18 August 2025 for randomised controlled trials and post hoc analyses of SGLT2 inhibitors reporting validated QoL or PRO outcomes in adults with T2DM. A random‐effects model was used to estimate mean differences (MD) or odds ratios (OR) with 95% CIs. Subgroup analyses compared SGLT2 inhibitors with placebo and active comparators. Risk of bias was assessed using the Cochrane RoB‐2 tool. Results Ten studies including 5294 patients (SGLT2i: 2807; control: 2487) were included. SGLT2 inhibitors significantly improved: EQ‐5D Index score versus placebo (MD: 0.04, p = 0.008), DTR‐QoL against active comparators (MD: 6.99; p = 0.0006), DTSQ compared to active comparators (MD: 0.54; p = 0.006) and IWQoL (MD: 1.44; p = 0.005) versus placebo. Improvements were also observed in SHIELD WQ‐9 overall QoL (OR: 2.11; p = 0.005), emotional health (OR: 2.16; p = 0.006), self‐esteem (OR: 2.26; p = 0.006) and work performance (OR: 1.99; p = 0.04) compared with placebo. Conclusion Randomised evidence suggests SGLT2 inhibitors enhance EQ‐5D Index score, diabetes‐specific QoL and several PROs in T2DM, particularly in physical, emotional and treatment satisfaction domains, supporting their earlier use in this population.