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Clinical outcomes in metastatic melanoma in Colombia: A retrospective cohort study from the REMMEC registry.
e21511 Background: Latin American melanoma data reflect distinct epidemiology and variable treatment access. REMMEC is a Colombian registry; survival estimates in stage IV disease remain limited. Methods: To characterize baseline features and first-line treatments and to evaluate overall survival (OS) and progression-free survival (PFS) in a Colombian metastatic melanoma cohort, we performed a retrospective cohort study of adults with stage IV melanoma in REMMEC (January 2011–June 2025) across multiple centers. Eligibility: histologically confirmed cutaneous or mucosal melanoma, distant metastases, age ≥18 years. Index date: stage IV diagnosis. OS was time from index to death; PFS was time from index to progression (RECIST v1.1 or investigator assessment) or death. Kaplan–Meier methods with log-rank tests compared groups. Cox models adjusted for age, sex, ECOG status, BRAF status, number of metastatic sites, and lactate dehydrogenase (reference: chemotherapy/other). Two-sided P<0.05 was significant. Multiple imputation for missing covariate data. Results: Mean age was 64 years (SD, 16); 55% male; 61% low-income. At initial presentation, 80% had stage IV disease. Primary site: cutaneous 70%, mucosal 30%; most common subtype was acral lentiginous melanoma (23%). BRAF testing was performed in 221 patients (61%), with mutations in 20% of those tested. First-line: immunotherapy monotherapy (n=161, 44%), dual-agent immunotherapy (n=54, 15%), BRAF/MEK inhibitors (n=22, 6%), chemotherapy/other (n=127, 35%). Adverse events 34% (any grade, CTCAE v5.0). Objective response 18.6% (complete 8.5%, partial 10.1%; RECIST v1.1). Median follow-up 29 months. Median OS 24 months (95% CI, 20–35); median PFS 21 months (95% CI, 18–26). Cutaneous melanoma: OS/PFS 32/25 months (95% CI, 24–58/20–32); mucosal melanoma: OS/PFS 19/17 months (95% CI, 13–NR/12–26; NR=not reached). By treatment—OS: immunotherapy 40 months (32–NR), BRAF/MEK 29 months (13–NR), chemotherapy/other 14 months (6–55); PFS: immunotherapy 32 months (25–40), BRAF/MEK 26 months (13–NR), chemotherapy/other 12 months (6–32). PFS events 167. Adjusted models showed improved OS and PFS with immunotherapy (OS HR 0.27 [95% CI, 0.15–0.49], P=0.001; PFS HR 0.35 [0.20–0.61], P=0.001). BRAF/MEK inhibitors were associated with longer OS (HR 0.43 [0.20–0.90], P=0.025) but not PFS (HR 1.36 [0.38–4.89], P=0.64; estimate imprecise due to small n). Metastatic burden ≥3 sites predicted shorter OS and PFS (OS HR 2.31 [1.30–4.11], P=0.004; PFS HR 2.21 [1.30–3.77], P=0.003). Conclusions: Immunotherapy was the predominant first-line approach and was associated with longer OS and PFS versus chemotherapy/other after adjustment. High stage IV and acral lentiginous prevalence support earlier detection strategies and expanded access to immune checkpoint inhibitors and targeted therapy.
Clinicopathological associations of p16 expression, high-risk HPV genotypes, and tumor-infiltrating lymphocytes on prognosis in anal squamous cell carcinoma.
e15503 Background: Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence worldwide. Chronic infection with high-risk human papillomavirus (HR-HPV) is a main etiologic factor. Viral oncoproteins E6 and E7 disrupt cell-cycle regulation, leading to p16 overexpression. Tumour-infiltrating lymphocytes (TILs) is a promising biomarker in solid tumors. Methods: We conducted a retrospective analysis of patients with ASCC treated with definitive chemoradiotherapy (CRT). We collected clinical and pathological data. Nuclear (N-p16) and cytoplasmatic p16 (C-p16) expression and TILs were assessed by immunohistochemistry and hematoxylin and eosin–stained sections. HR-HPV status was determined using a PCR-based commercial assay. Survival was analyzed using Kaplan–Meier and Cox models. Results: 86 patients (pts) were included; median age: 57 years (IQR, 47–66), 60% were female, and 88% had ECOG performance status 0–1. Poorly differentiated tumors were observed in 31%, nodal involvement in 69%, and stage III–IV disease in 78% (stage IV due to inguinal nodal involvement). Most patients received CRT (88%), achieving an objective response in 76%. HPV was positive in 90% of evaluable cases, with high-risk genotypes detected in 54%. High N-p16 and C-p16 expression ( > 70%) was observed in 53% and 47%, respectively. Stromal TILs (s-TILs) (73 pts), with a median of 10% (IQR, 5–30); 49% had high s-TILs ( > 10%). After a median follow-up of 58.1 months, median event-free survival (EFS) was 50.4 months (95% CI, 18.6–82.3), while median overall survival (OS) was not reached. In multivariable Cox regression, stage III–IV disease (HR 6.58, 95% CI 1.52–28.44; p = 0.012) and N-p16 low expression (HR 2.50, 95% CI 1.20–5.00; p = 0.013) remained independently associated with inferior EFS. Complete response (CR) after CRT was associated with improved OS (HR 6.64, 95% CI 2.00–21.00; p = 0.001). High N-p16 expression was significantly associated with complete response after CRT (OR = 4.71; 95% CI 1.43–18.68; p = 0.015). Conclusions: In addition to clinical stage p16 expression is a key prognostic biomarker associated with event-free survival and may be useful for risk stratification in patients with ASCC treated with chemoradiotherapy. Characteristic N = 86 1 AgeMedian (Q1–Q3) 57.00 (47.00–66.00) GenderFemale 52(60%) Clinical Stage (AJCC 7 th ed)Stage I–IIStage III-IV 19 (22%)67 (78%) HPV statusPositiveNegativeUnknown 74 (90%)8 (9.8%)4 Nuclear p16 expression High (>70%)Low (<=70%)Unknown 37(53%)33(47%)16 Stromal TILs (sTILs)Median(Q1–Q3) (n=73) 10.00 (5.00–30.00) Response after treatment Partial or completeStable or Progression 65(76%)21(24%) Events (progression or death)Progression or deathDeathCensored 43 (50%)15 (17%)43(50%) Outcomes (median, months)EFSOSFollow-up 50.4Not-reached.58.1
Efficacy and safety of TACE combined with immune checkpoint inhibitors and VEGF inhibitors in hepatocellular carcinoma: A systematic review and meta-analysis.
e16300 Background: Transarterial chemoembolization (TACE) remains the standard of care for intermediate stage hepatocellular carcinoma (HCC), yet long term survival is limited by high rates of recurrence and progression. The addition of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) with TACE has recently emerged as a promising strategy. This meta-analysis evaluates the efficacy and safety of TACE plus systemic combination therapy compared to TACE alone. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Studies evaluating TACE combined with dual systemic therapy (ICI + TKI/VEGF inhibitor) were identified through major databases up to January 2026. Pooled odds ratios (ORs) and Hazards Ratio (HRs) were calculated using fixed effects models as appropriate. Results: Five studies (4 RCTs, 1 cohort) comprising 1964 patients were included. Progression-free survival was significantly longer with TACE combined with dual systemic therapy compared with TACE alone (mean difference 4.12 months, 95% CI 2.86-5.37; p < 0.00001; I² = 73%). The objective response rate was also significantly higher with TACE combination therapy (OR 2.66, 95% CI 2.17-3.26; p < 0.00001), despite substantial heterogeneity (I² = 83%). Grade 3/4 adverse events were significantly more frequent with TACE combination therapy (OR 3.36, 95% CI 2.66-4.25; p < 0.00001; I² = 68%). The most common severe toxicities included Hypertension (16.2%), Immune-mediated Hepatitis (9.6%), and Proteinuria (8.8%). Hypertension occurred significantly more often with TACE combination therapy than with TACE alone (pooled OR 9.52, 95% CI 1.83-49.62; p = 0.007; I² = 51%). Conclusions: The addition of ICI and TKI/VEGF inhibitors to TACE provides consistent, statistically significant and clinically meaningful improvement in disease control for unresectable HCC. This can be explained on the basis of complementary biological mechanisms, including enhanced tumor antigen exposure following TACE, restoration of antitumor T cell activity with ICI, and suppression of TACE induced angiogenesis through VEGF pathway blockade. While the efficacy benefit is robust across trials, safety profiles vary significantly by regimen.The higher rate of grade ¾ adverse effects, especially hypertension and immune-mediated hepatitis, is mainly due to the biological effects of VEGF inhibitors on blood vessels and the increased immune activation caused by immune checkpoint inhibitors. Despite a higher incidence of grade 3/4 toxicities, adverse events were generally manageable with standard supportive care and dose modifications. Overall, these findings support the use of TACE-systemic combinations as a new potential standard of care, with careful patient selection and toxicity monitoring.
Screen failure and treatment dropout in oncology clinical trials: A multicenter analysis from Türki̇ye.
e23009 Background: Screen failure and treatment dropout remain major barriers to successful conduct of oncology clinical trials, particularly in real-world, middle-income settings. Data evaluating both patient- and center-related factors influencing screen failure, dropout, and time to dropout are limited. Methods: This multicenter retrospective analysis included 1,229 oncology patients screened for clinical trials across 13 centers in Türkiye. Causes of screen failure and dropout were descriptively analyzed. Time to dropout was assessed using median values and compared across subgroups using the Mann–Whitney U and Kruskal–Wallis tests. Results: Overall, 1,155 patients experienced screen failure, and 74 patients dropped out after trial initiation. Patients with screen failure had a median age of 64 years, and 67.3% were male. The most frequent cancer types among screen failure patients were lung (57.0%), breast (13.7%), and prostate cancer (8.6%). The primary causes of screen failure in the overall cohort were non-fulfillment of inclusion criteria (69.4%), presence of exclusion criteria (21.4%), and patient non-compliance (4.1%). Among the 74 patients who dropped out, 63.5% were male, with a median age of 62 years; the most common diagnoses were lung (44.6%), gastric (27.0%), and breast cancer (23.0%). The leading causes of dropout were adverse events (33.8%), disease progression (28.4%), and patient dissatisfaction (14.9%). Median time (months) to dropout was significantly shorter in female patients (3 vs 7, p = 0.014), patients without comorbidities (7 vs 8, p = 0.036), those treated in neoadjuvant or adjuvant compared with metastatic settings (7.5 vs 6.5 vs 8, p < 0.001), patients receiving parenteral compared with oral or oral plus parenteral regimens (7 vs 9.5 vs 13, p = 0.035), and in centers with a clinical research unit or a clinical research center compared with centers without an administratively organized unit (7 vs 6.5 vs 10, p = 0.010). Finally, time to dropout decreased with increasing sub-investigator research experience, defined as the total number of clinical trials in which the sub-investigator had previously participated (0–5, 6–10 and > 10 trials, respectively; median 9.5 vs 7 vs 5 months; p = 0.022). Principal investigator experience and total trial volume per center were not associated with time to dropout. Conclusions: In this multicenter study, screen failure in clinical trials was predominantly driven by eligibility criteria, while treatment dropout was mainly related to toxicity and disease progression. Time to dropout varied according to patient characteristics, treatment setting, route of administration, and center-level factors, underscoring the influence of both clinical and operational elements on trial retention. These findings highlight the importance of pragmatic trial design and strengthened research infrastructure to improve feasibility and retention.
HopeMove: Feasibility and acceptability of a mobile exercise app for pediatric patients undergoing cancer treatment.
10034 Background: Cancer related fatigue and reduced physical activity are common during pediatric cancer treatment and negatively affect daily functioning and quality of life. Although exercise is recommended as supportive care, maintaining regular physical activity during active treatment is challenging. Digitally delivered exercise programs may offer flexible and safe supportive care options. This study evaluated the feasibility, acceptability, usability, and safety of the HopeMove mobile exercise app and explored preliminary changes in fatigue among adolescents undergoing cancer treatment. Methods: This prospective, single center pilot feasibility study included adolescents aged 13-18 years undergoing active cancer treatment (N=15). Participants completed 45 minute video guided exercise sessions at least three times per week for eight weeks. The intervention was developed through a multidisciplinary collaboration involving pediatric oncology clinicians, pediatric nurses, physiotherapists, and engineers. Exercise sessions included warm-up, aerobic, strengthening, flexibility, and cool down components, with seated and standing options tailored to individual clinical needs. Prior to patient implementation, the HopeMove mobile application was evaluated by 10 clinical experts using the Mobile Application Usability Scale (MAUS). Feasibility outcomes included recruitment, retention, adherence, and technical performance. Adherence was defined as completing at least 75% of planned exercise sessions. Participant satisfaction was measured with a Visual Analog Scale (VAS). Before the intervention, adolescents completed brief application evaluation questions. Fatigue was assessed before and after the intervention using a validated pediatric oncology specific fatigue scale. Safety was monitored throughout the study. Results: All eligible adolescents agreed to participate and completed the intervention, resulting in 100% recruitment and retention. Twelve participants (80%) met adherence criteria. The application showed high usability (mean MAUS score 6.55±0.49) and high satisfaction (VAS mean 6.66±0.48). Participants reported the application to be easy to use and age appropriate. Fatigue scores improved significantly after the intervention, increasing from 100.06±22.28 at baseline to 139.26±18.89 post-intervention (p<0.001). Significant improvements were observed across fatigue subdomains (all p<0.01). No exercise related adverse events, injuries, falls, or treatment interruptions were reported. Conclusions: HopeMove was feasible, acceptable, and safe for adolescents undergoing active cancer treatment. High adherence, favorable usability, and improved fatigue outcomes suggest that mobile, video guided exercise interventions may support supportive care in pediatric oncology. Larger controlled studies are warranted. Clinical trial information: NCT07274358 .
Stereotactic body radiotherapy plus cadonilimab and lenvatinib as conversion therapy for potentially resectable hepatocellular carcinoma (UniRTX): A phase II study.
e16278 Background: Successful conversion to resectability may improve survival in patients with potentially resectable hepatocellular carcinoma (HCC), while effective conversion strategies remain limited. This study evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with cadonilimab, a PD-1/CTLA-4 bispecific antibody, and lenvatinib as a conversion regimen. Methods: This prospective, single-arm, phase II study enrolled patients with pathologically confirmed HCC considered potentially resectable, defined as macrovascular invasion (portal vein, hepatic veins, or inferior vena cava), or tumor number plus largest diameter > 7 and baseline AFP > 400 μg/L, excluding patients suitable for upfront surgery or with extrahepatic metastasis. Patients received SBRT (18–40 Gy in 3–5 fractions), followed by cadonilimab (10 mg/kg IV Q3W) plus lenvatinib (8 mg PO QD) for 4 cycles. Multidisciplinary assessment determined curative-intent therapy or continuation of systemic treatment. The primary endpoint was objective response rate (ORR) per RECIST v1.1 and mRECIST. Secondary endpoints included conversion rate, pathological complete response (pCR) rate, major pathological response (MPR; ≤30% residual viable tumor) rate, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From April 18, 2023, to November 14, 2025, enrollment was completed with 30 patients. The median age was 55.5 years, and 73.3% (22/30) had BCLC stage C, with 26 patients undergoing at least one post-baseline radiologic assessment. According to RECIST v1.1, the ORR and DCR were 73.1% (19/26) and 92.3% (24/26), respectively. Based on mRECIST, the complete response (CR) rate, ORR, and DCR were 11.5% (3/26), 80.8% (21/26), and 92.3% (24/26), respectively. Successful conversion was achieved in 18 patients (69.2%, 18/26). Fifteen patients (57.7%, 15/26) proceeded to curative-intent therapy (resection, n = 12; radiofrequency ablation, n = 3), and 3 patients declined surgery. Among resected patients, the pCR and MPR rates were 41.7% (5/12) and 83.3% (10/12), respectively, with R0 achieved in all surgical cases. At the data cutoff of January 5, 2026, the median follow-up was 15.5 months (95% CI, 10.0–27.2). Median PFS was 18.2 months (95% CI, 13.5–NA), and median OS was not reached. All patients experienced treatment-related adverse events (TRAEs) of any grade. Grade ≥3 TRAEs occurred in 26.7% (8/30) of patients, including anaphylaxis, increased ALT/AST, neutropenia, leukopenia, hand–foot syndrome, and gastrointestinal ulcer. No treatment-related deaths or radiation-induced liver disease were observed. Conclusions: SBRT plus cadonilimab and lenvatinib showed encouraging efficacy and manageable toxicity as a conversion strategy for potentially resectable HCC. Clinical trial information: ChiCTR2300068781.
Patterns of chemotherapy delivery following neuropathy in patients with stage I-IIIA breast cancer.
e12514 Background: Chemotherapy-induced neuropathy is a common toxicity during treatment for breast cancer and may prompt changes in chemotherapy delivery, including a reduction in cumulative dose or dose intensity, which are associated with worse breast cancer outcomes. Real-world patterns of chemotherapy delivery following neuropathy and associated patient- and provider/facility-level factors remain poorly characterized. Methods: We analyzed data from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study of women with primary stage I–IIIA breast cancer diagnosed between 2005-2019 who received adjuvant chemotherapy at Kaiser Permanente Northern California (KPNC) or Washington (KPWA) and developed chemotherapy-induced neuropathy during treatment. Neuropathy was identified using diagnostic codes and clinical documentation. The primary outcome was defined as chemotherapy modification in the cycle following neuropathy identification, including dose reduction ≥10%, regimen change, or chemotherapy discontinuation. Multivariable generalized linear models of the Poisson family were used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for patient- and provider/facility-level factors (e.g., provider gender, practice size, treatment facility urbanicity (defined as 100% urban vs < 100% urban)) associated with the composite outcome. Provider/facility analyses were limited to KPNC sub-cohort. Results: Among 3,801 patients on chemotherapy who developed neuropathy, 12.9% experienced a chemotherapy modification in the subsequent cycle. The most common modification was dose reduction ≥10% (11.3%), followed by regimen change (2.4%), and early discontinuation (0.8%). The likelihood of modification increased with age (p-trend < 0.001), particularly among patients aged ≥75 years versus < 40 years (aPR 3.01; 95% CI 1.76–5.35). Other patient factors associated with any chemotherapy modification included HER2-positive disease (aPR 1.69; 95% CI 1.24–2.30), pre-existing liver disease (aPR 1.73; 95% CI 1.09–2.72), and receipt of dose-dense chemotherapy (aPR 1.69; 95% CI 1.24–2.30). Chemotherapy agent type was also associated with the likelihood of subsequent modification. Among provider/facility factors, treatment at non-urban facilities was associated with higher likelihood of chemotherapy modification (aPR 1.86; 95% CI 1.25-2.76). No other provider or facility factors were associated with chemotherapy modification. Conclusions: Chemotherapy delivery after neuropathy varied by patient, treatment, and facility characteristics, underscoring the complexity of treatment decisions following toxicity and the need to better characterize factors influencing chemotherapy delivery in real-world practice.
Molecular characterization of residual disease post-neoadjuvant sacituzumab govitecan (SG), pembrolizumab, or their combination in patients with muscle-invasive bladder cancer (MIBC).
4617 Background: In patients (pts) with MIBC, we tested the activity of neoadjuvant SG (SURE-01, NCT05226117), SG + pembrolizumab (SURE-02, NCT05535218) and pembrolizumab alone (PURE-01, NCT02736266), followed by surgery. We aimed to molecularly characterize the residual post-neoadjuvant therapy (NAT) MIBC and its changes from baseline samples. Methods: Post-NAT samples (ypT≥2) were available for transcriptome analyses from 12 pts in SURE-01, 24 in SURE-02, and 26 post-pembrolizumab alone. Decipher bladder genomic subtyping classifier (GSC) expression profiling assay (Veracyte) was used to compare molecular subtyping distributions and genes/signatures expressions between matched pre-post NAT samples, including 192 locked transcriptomic signatures in GRID (v3.1) and pre-specified therapeutic target genes. FGFR3-active tumors were determined using a previously-developed long non-coding RNA (lncRNA)-based classifier. The clinical primary endpoint was event-free survival (EFS). Results: Post-NAT molecular subtyping identified Luminal (L) vs non-Luminal (NL) tumors in: 17% (2/12) vs 83% (10/12) (SURE-01), 21% (5/24) versus 79% (19/24) (SURE-02), and 8% (2/26) versus 92% (24/26) (PURE-01). In total, 21 pts from SURE studies and 22 from PURE-01 had matched pre-post NAT samples. Consensus molecular subtyping revealed a concordance in 86% (6/7) of pts in SURE-01, 57% (8/14) in SURE-02 and 36% (8/22) in PURE-01. Stroma-rich tumors were found in 17% (2/12), 29% (7/24) and 50% (13/26) of post-NAT samples. After NAT, we found a decrease in L subtypes in SURE-01 (57% → 29%) and in SURE-02 (36% → 14%) vs an increase in stroma-rich (Consensus) subtype in SURE-02 (7% → 36%) and in PURE-01 (14% → 50%). Elevation of TGF-beta signaling hallmark (p=0.02) and immune exclusion (p=0.02) scores characterized post-NAT samples in SURE-01, while in SURE-02 we found elevated stromal gene scores (p=0.004) and lower DNA repair hallmark scores (p=0.03) after NAT. Comparing matched samples from SURE-01 and 02, we found significantly decreased TROP2 expression scores (p=0.03) and lower HER2 (p=0.06) and NECTIN4 expression (p=0.07). Application of the lncRNA-based FGFR3-activity classifier revealed a total of 10/36 (28%) FGFR3-active tumors post-NAT in SURE-01 and SURE-02, all without EFS events during follow-up. For SURE-02, we found 4/24 (17%) pts harboring claudin-low tumors post-NAT, who did not experience EFS events following adjuvant pembrolizumab, similar to the low EFS rate observed in PURE-01 (N=7, 22%). Conclusions: This study expands our knowledge on residual MIBC after various NAT, displaying a noteworthy plasticity and significant changes post-NAT that are important to unveil the biology of these tumors and putative biomarkers for sequential therapies.
Imneskibart + low-dose subcutaneous IL-2 ± nivolumab in patients with CPI-refractory cutaneous melanoma: Promising results from an ongoing phase 1/2 study.
9526 Background: Imneskibart (AU-007) is an AI designed monoclonal antibody binding to interleukin-2 (IL-2) preventing binding to CD25 in the trimeric IL-2 receptor (IL-2 R), while allowing engagement with the dimeric IL-2R, CD122/CD132. Imneskibart-bound IL-2 expands T effector (Teff) and NK cell populations (dimeric IL-2R) without expanding regulatory T cells (Tregs; trimeric IL-2R). Methods: Patients (pts) with locally advanced/metastatic cutaneous melanoma were evaluated in Phase 1 (Ph1) dose escalation and in 2 ongoing Ph2 expansion cohorts. Rigorous eligibility criteria were applied requiring pts to have objective progression after ≥ 2 cycles of prior doublet checkpoint inhibitors (CPI, anti-PD-1 + anti-CTLA-4 or anti-LAG-3) with confirmation of progression ≥ 4 weeks later. Ph2 Cohort 1 evaluated the recommended Ph2 dose (RP2D) of 9 mg/kg imneskibart IV Q2W. Ph 2 Cohort 2 evaluates the RP2D of imneskibart IV Q2W + nivolumab (nivo) 480 mg Q4W. Both cohorts receive subcutaneous (SC) 135K IU/kg aldesleukin dose on Day 1 of first cycle with additional doses of aldesleukin administered at the beginning of each cycle until at least a partial response (PR) is obtained. Tumor reassessment is performed at the end of each 8-week cycle. Results: Fifteen pts received imneskibart + aldesleukin: 2 in Ph1 and 13 in Ph2. Fourteen pts were efficacy evaluable. Nine pts had tumor reductions ranging from -1 to -100% including pts with -100% and -58% reductions (continue treatment at 24 and 18 M respectively), and a -48% reduction (14 M on treatment). The median PFS and duration on treatment were 7.6 and 9 M respectively (9.3 M median follow up); 6 pts continue treatment. Nine of 14 evaluable pts have received imneskibart + IL-2 for a longer duration than their prior CPI doublet therapy. Eight pts enrolled in Ph2 Cohort 2 and 2 of the 6 efficacy evaluable pts to date (33%) had PRs with -35% and -31% tumor reductions and continue treatment. Two of 6 had SD and continue treatment. Overall, 67% had disease control at 4 months. Six pts continue treatment. Imneskibart led to a decrease in peripheral Tregs and increase in CD8 cells leading to CD8/Treg ratio increases up to 2 – 3 fold over BL. CD8/Treg ratio increases > 2 fold over BL were associated with longer median duration on treatment, PFS, and OS. Imneskibart + IL-2 was well-tolerated with Grade 3/4 drug-related adverse events (AE) occurring in only 14% of pts and in 0 of the 8 pts who received this combination + nivo. No patient discontinued treatment due to a drug-related AE. Conclusions: Compelling anti-tumor activity is observed with imneskibart + IL-2, with a strong emerging signal of enhanced activity with the nivolumab combination in pts with melanoma refractory to doublet CPI therapy. Imneskibart + IL-2–associated Treg reduction likely drives the high disease control rate, supporting durable benefit with prolonged treatment exposure and PFS. Clinical trial information: NCT05267626 .
Cost-effectiveness of post-discharge home care for reducing potentially avoidable readmissions in stage IV cancer.
12031 Background: Approximately 39% of hospital readmissions among stage IV cancer patients are potentially avoidable. These readmissions increase healthcare costs, reduce quality of life, and increase mortality. Home-based care may reduce avoidable readmissions through symptom management and care coordination, but cost-effectiveness in this population remains unknown. Objective: To evaluate the cost-effectiveness of home with care versus home without care for stage IV solid tumors patients post-discharge, from an Ontario public payer perspective. Methods: A four-state Markov model (Care, Readmission, Discharged, Death) was developed with week-long cycles with a 180 day horizon. Weekly potentially avoidable readmission rates were 1.8% (home with care) versus 5.4% (home without care). Utilities (0.65 vs 0.55) and costs (home care $100/day; readmission $994/day) were from Canadian sources. Primary outcome was incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way, two-way, and probabilistic sensitivity analyses (1,000 simulations) were conducted. Value of information analysis quantified decision uncertainty. Costs and QALYs were discounted at 1.5% annually. Results: Home with care produced 0.166 QALYs at $12,251 versus 0.105 QALYs at $7,386, yielding 0.061 incremental QALYs (22 quality-adjusted days) at $4,865 incremental cost (ICER: $79,955/QALY). Home care cost was the most influential cost parameter with a threshold of $115/day. Probabilistic analysis showed 60% probability of cost-effectiveness at willingness-to-pay (WTP) $100,000/QALY, with acceptability curves crossing at $80,000/QALY. Expected value of perfect information peaked at $1,500/patient. Conclusions: Home with care may represent a cost-effective option for stage IV cancer patients at or below the commonly accepted Canadian WTP threshold of $100,000/QALY, with robust findings across sensitivity analyses. Program costs are the primary value determinant, supporting policy consideration for post-discharge support services. Cost-effectiveness results: Home with care versus home without care. Outcome Home with Care Home without Care Difference Total cost $12,251 $7,386 +$4,865 Total QALYs 0.166 0.105 +0.061 Quality-adjusted days 60.6 38.3 +22.3 ICER — — $79,955/QALY Probability cost-effective at WTP $100,000/QALY 60% 40% — QALY = quality-adjusted life-year; ICER = incremental cost-effectiveness ratio; WTP = willingness-to-pay. Costs in 2024 Canadian dollars.
Ultra–early-onset metastatic colorectal cancer (<35 years): RAS-driven, APC/TP53-depleted, TMB-low molecular features in a real-world analysis of 2,392 patients.
3542 Background: Early-onset colorectal cancer (CRC, <50 years) is on the rise globally and includes a biologically heterogeneous disease. Patients diagnosed before age 35 represent the extreme of early-onset CRC, yet their clinical and genomic features remain poorly understood. We investigated whether ultra–early-onset metastatic CRC (UEO-CRC, <35 years) exhibits distinct outcomes and a unique molecular profile in a large real-world cohort. Methods: We analyzed a multicenter cohort of 2,392 patients with metastatic CRC; 1,612 had comprehensive genomic profiling (Foundation Medicine) and were included in molecular analyses. Patients were classified as ≤35 years (n=130) or >35 years (n=1482) at metastatic diagnosis. Overall survival (OS) was assessed using Kaplan–Meier estimates and log-rank tests. Gene- and pathway-level differences were evaluated using Fisher’s exact test. A composite UEO-CRC molecular signature was defined based on features significantly enriched or depleted in patients <35 years. Results: UEO-CRC represented 8.1% of metastatic cases. Patients ≤35 years had significantly worse survival than those >35 years (median OS 35.0 vs 46.0 months; p=0.0081). Molecular profiling revealed a distinct oncogenic pattern characterized by: enrichment of RAS mutations (KRAS 48.6% vs 36.4%, p=0.011; NRAS 11.7% vs 4.1%, p=0.0011); marked depletion of APC (21.6% vs 63.4%, p<0.001) and TP53 mutations (33.3% vs 63.8%, p<0.001); suppression of WNT pathway alterations (25.2% vs 66.9%, p<0.001); and genomic stability without hypermutation, including absence of TMB-high tumors (0% vs 7.5%, p=0.00037), lower median TMB (3.1 vs 4.8 mut/Mb, p<0.001), no MSI-H cases, and rare POLE/POLD1 or DDR alterations (4.5% vs 1.2%, p=0.017). Integration of these features identified a reproducible UEO-CRC molecular signature (RAS-mutant, APC/TP53 wild-type, TMB-low), over six-fold more frequent in UEO-CRC than in patients ≥35 years (32% vs 5%; p<0.001). Conclusions: Ultra–early-onset metastatic CRC (<35 years) represents a biologically aggressive and genomically distinct entity. UEO-CRC is defined by a non-canonical, RAS-driven, APC/TP53-independent tumorigenic program occurring without hypermutation, MSI-H, or POLE-driven biology. The lack of TMB-high indicates limited immunogenicity, emphasising the need for age-specific biological stratification and customised therapeutic strategies in this high-risk population.
Single cell analysis of recurrent/metastatic, platinum resistant nasopharyngeal cancer patients treated within the POINT trial: Transitional insights for future research.
e18028 Background: POINT trial treated platinum-resistant, recurrent/metastatic (RM) Nasopharyngeal Carcinoma (NPC) patients (pts) with pembrolizumab and olaparib combination. To explore mechanisms of treatment sensitivity/resistance, we performed a translational analysis on selected pts who got opposite treatment response as excellent or poor. Methods: We retrieved baseline FFPE samples of 4 good responders -R- (pts obtaining clinical benefit with partial response or long-lasting stable disease), and 4 non-responders -NR- (progression within 4 months since treatment start), matched-paired for age, ECOG performance status, baseline plasma EBV DNA load, and disease burden/subsites. Samples were processed through Chromium X and libraries were sequenced on NextSeq 2000 platform (Illumina). Single cell data analysis was performed using Seurat (v5.3.1). Results: Patient’s characteristics are reported in Table 1. Immune and stromal cell types, identified based on transcriptomic profile, exhibited distinct proportional differences between R and NR. In R, T cells were enriched for gene signatures associated with migration, cytotoxicity, and active metabolic states; tumor epithelial cells’ phenotype, expressing IDO1 , PROX1 and CXCL14 , was consistent with a microenvironment actively supporting immune response. In contrast, NR T cells showed increased expression of chronic activation state genes, MAP4K1 , ZAP70 , and PIK3CD ; tumor epithelial cells displayed a more aggressive transcriptional profile, marked by signatures of invasion, epithelial–mesenchymal transition, extracellular matrix remodeling and immune suppression. Furthermore, B cells from responders to the treatment express tertiary lymphoid structure’s markers, such as CXCR5. Validation of these findings is ongoing through spatial transcriptomics. Conclusions: We highlighted clear differences in both cellular composition and gene expression profiles between R and NR baseline samples from platinum-resistant NPC pts treated with an immunotherapy-based approach. These preliminary findings provide novel insights on treatment selection of NPC pts and on future improvements in therapeutic strategies for resistant pts. Clinical trial information: NCT04825990 . Patients 1-R 1-NR 2-R 2-NR 3-R 3-NR 4-R 4-NR Plasma EBV DNA (copies/ml) 732 441 181 24 6341 7020 1258 1429 Disease sites Local Local, bone Hepatic Hepatic, bone Local, hepatic Hepatic, bone, nodal Pleural Distant nodal Sex M M F F M M F M Age (years) 51 62 55 51 40 42 69 40 ECOG PS 0 0 0 0 0 0 0 0 PFS (months) 9 4 17 2 15 2 20 4
A phase 1 study of the PRMT5 inhibitor AZD3470 in patients with relapsed/refractory classic Hodgkin lymphoma (PRIMAVERA).
7003 Background: The epigenetic enzyme protein arginine methyltransferase 5 (PRMT5) plays a critical role in cell proliferation and differentiation; PRMT5 dysregulation is associated with cancer development. Methylthioadenosine (MTA) is an endogenous partial inhibitor of PRMT5 that accumulates in cancer cells deficient in MTA phosphorylase (MTAP). In classic Hodgkin lymphoma (cHL), we previously reported that >80% of primary patient (pt) tumor samples are MTAP deficient (Urosevic J, ASH 2023). The MTA-cooperative PRMT5 inhibitor AZD3470 preferentially binds to the MTA-bound state of PRMT5, increasing its target engagement to MTAP-deficient cancer cells. Here, we present safety and preliminary efficacy of AZD3470 from a first-in-human Phase 1 study in relapsed/refractory (r/r) cHL (NCT06137144). Methods: Eligible pts were ≥18 years with r/r cHL after ≥3 prior lines of therapy (including brentuximab vedotin (BV) and anti-PD-1). In dose escalation, pts received oral AZD3470 monotherapy QD in ascending dose levels (DLs) using an mTPI-2 design. Primary endpoints were incidence and severity of treatment-emergent adverse events (TEAEs) and dose-limiting toxicity (DLT). Secondary endpoints were overall response rate (ORR) and complete response rate (CRR) per Lugano 2014 criteria. Results: As of Nov 25, 2025, 39 pts had received AZD3470 at DLs ranging from 1 to 8. Most pts were male (62%) with stage IV disease (77%) and a median age of 42 (range 25–78) years. Pts had received a median of 6 prior lines of anticancer therapy (range 3–14); all had had prior BV and anti-PD1 treatments, and 20 (51%) and 5 (13%) pts had had prior autologous and allogeneic hematopoietic stem cell transplantation, respectively. All patients evaluable for MTAP protein expression were MTAP deficient. Median duration of exposure was 15 weeks (range 0.1–45.1), with treatment ongoing in 16 pts (41%). TEAEs occurred in 85% of pts, predominantly grades 1 or 2. The most common TEAEs (any grade) were anemia (28%) and nausea (15%), followed by asthenia, constipation, fatigue, and neutropenia (13% each). Grade ≥3 TEAEs occurred in 28% of pts, most commonly neutropenia (related) and hypokalemia (n=2 each). Serious TEAEs occurred in 5 (13%) pts. Two pts had dose reductions due to TEAEs (grade 4 hypertriglyceridemia and grade 3 esophagitis). No DLTs, treatment discontinuations nor deaths due to TEAEs were reported. Of the 31 pts evaluable for efficacy, 14 had an objective response, with responses at doses ≥DL4. The highest response rate was observed at doses ≥DL7 (n=10) with an ORR of 80% and CRR of 50%. Conclusions: AZD3470 monotherapy was well tolerated up to DL8, with no DLTs and mainly low-grade AEs. Incidences of grade ≥3 AEs and SAEs were low. Importantly, both the ORR and CRR were dose-dependent and notably high in this heavily pretreated cHL population. Dose optimization is ongoing and further safety and efficacy will be reported. Clinical trial information: NCT06137144 .
A pilot study exploring four meditation practices for anxiety among cancer survivors.
e24132 Background: Meditation has been associated with reductions in anxiety among cancer survivors. This study aims to evaluate four meditation techniques for reducing anxiety after acute stress in cancer survivors. Methods: Cancer survivors without significant meditation experience treated with surgery alone were randomized to one of the four arms: breathing, focused attention, mindfulness, or a combination. Participants learned the assigned meditation technique over 3 weeks. At baseline (V1) and the final visit (V5), subjects underwent the Trier Social Stress Test (TSST) and completed the Spielberger State-Trait Anxiety Inventory-Short Form (STAI-SF) questionnaire, visual analog scale 0-10 (VAS) of anxiety, salivary α-amylase, and systolic blood pressure (SBP) at different time points including before TSST (T3), after TSST (T4), and after meditation post-TSST (T5). Paired t-tests assessed within group pre-post differences and across timepoints in VAS-Anxiety, amylase, and SBP scores. A mixed effects model was used for STAI scores. Results: A total of 29 subjects (accrual goal 44) completed the study (median age 64 years; 72% male). Cancer types include prostate (66%), thyroid (17%), bladder (7%), kidney (7%), and skin (3%). Our preliminary results show the combination group had a significant decrease in VAS-Anxiety after meditation post-TSST from V5 T4-T5 (-3.1, p = 0.02), while the breathing group (-2.2, p = 0.08) and mindfulness group (-2.1, p = 0.08) were nearing significance. The combination group also had significant reductions in VAS-Anxiety between V1-T4 and V5-T4 (-3.7, p = 0.01), and near significance between V1-T5 and V5-T5 (-2.4, p = 0.052). The mindfulness group showed a significant decrease in amylase post-TSST between V1-T4 and V5-T4 (-301, p = 0.04), and near significant decrease between V1-T5 and V5-T5 (-261, p = 0.059). The breathing group showed a significant decrease in SBP across timepoints between V1 and V5 (p = 0.001). Across all study arms, there was an overall decrease in STAI scores at V5 compared to V1 (p = 0.0002). The planned study completion is in Summer of 2026. Conclusions: With this brief 3-week intervention of four types of meditation, only the combination group showed significant changes in the primary aim of VAS-Anxiety after acute stress. The mindfulness and breathing groups may work through different physiological mechanisms to counter stress and thus may explain why a combination approach is most effective. Clinical trial information: NCT06500377 .
Overall survival association of adjuvant endocrine therapy (ET) after pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in ER+/HER2+ early-stage breast cancer.
541 Background: In ER+/HER2+ early breast cancer, adjuvant ET is standard; however, its survival benefit for patients achieving pCR after NAC remains uncertain. As pCR is associated with favorable prognosis and may inform postoperative decision-making, it is unknown if pCR identifies a subset in whom the ET survival benefit is reduced. We evaluated ET use patterns and its association with overall survival (OS) in ER+/HER2+ patients with pCR after NAC. Methods: Using NCDB, we identified women with ER+/HER2+ M0 breast cancer treated with NAC and definitive surgery (2018-2022) who achieved pCR (ypT0/ypTis and ypN0). The primary endpoint was OS. To reduce immortal time bias, we used a time-varying Cox model with ET initiation as a time-dependent exposure (time zero: surgery). A 6-month landmark analysis was performed as a sensitivity analysis. Multivariable models adjusted for demographic, clinicopathologic, treatment, and socioeconomic variables. Predictors of ET omission were assessed using multivariable logistic regression. Exploratory analyses evaluated ER-low (1-10%) and effect modification using an ET×ER-low interaction term. Results: Of 8,981 patients, 7,917 (88.2%) received ET and 1,064 (11.8%) did not. In the time-varying Cox model, ET receipt was associated with improved OS (HR 0.79, 95% CI 0.67-0.93). Worse OS was associated with older age (per 10 years: HR 1.17, 95% CI 1.10-1.24) and stage III disease (HR 1.39, 95% CI 1.16-1.67). In 6-month landmark analysis (n=8,756), ET benefit persisted (HR 0.58, 95% CI 0.39-0.86). There was no differential association by ER-low status (ET×ER-low interaction p =0.73), with similar ET associations in ER-high (HR 0.58) and ER-low (HR 0.63) groups. ET was omitted in 36.9% of ER-low patients compared to only 7.6% of ER-high patients. Logistic regression identified ER-low status as the strongest predictor of ET omission (OR 0.16, 95% CI 0.14-0.19). Omission was also more likely with older age (per 10-year increase: OR 0.92, 95% CI 0.85-0.99) and community facility treatment (OR 0.74, 95% CI 0.55-0.99), while ET receipt was more likely with PR-positivity (OR 1.54, 95% CI 1.32-1.79), radiation (OR 2.78, 95% CI 2.32-3.33) and HER2-targeted therapy (OR 2.62, 95% CI 2.03-3.38). Conclusions: In this NCDB cohort, adjuvant ET was associated with improved OS in ER+/HER2+ patients achieving pCR after NAC. The survival association did not differ by ER-low status, though event rates in this subgroup were limited. ER-low status was the strongest predictor of ET omission, highlighting a potential gap between real-world practice and outcomes. These findings support continued consideration of ET in post-pCR ER+/HER2+ patients, including the ER-low population. Cohort Total N ET (%) No ET (%) Death (%) Overall 8,981 7,917 (88.2%) 1,064 (11.8%) 152 (1.7%) ER-low 1,316 831 (63.1%) 485 (36.9%) 32 (2.4%)
Impact of multidisciplinary rounds on time to treatment for veterans with lung cancer at a VA medical center.
e23281 Background: Delays in initiating lung cancer treatment adversely affect patient outcomes. In late 2024, increasing delays at our center were associated with care coordination gaps during periods of navigator turnover. To address these barriers, weekly multidisciplinary rounds (MDR) were implemented in February 2025. Methods: We conducted a retrospective review of Veterans with newly diagnosed lung cancer who had an oncology consult placed between November 4, 2024, and January 30, 2025. Prior to intervention design, a multidisciplinary root cause analysis using an Ishikawa diagram was performed to identify system-level contributors to treatment delays. The intervention consisted of a weekly, one-hour virtual multidisciplinary round held immediately after thoracic tumor board, involving medical oncology, pulmonary medicine, radiation oncology, surgery, nursing, and care coordination staff. During these sessions, patients were reviewed to identify and address delays in diagnostic completion, consult placement, treatment sequencing, and external referrals, with real-time assignment of next steps and responsible services. Patients treated prior to MDR implementation comprised the pre-intervention group (n = 25), while those managed after MDR initiation formed the post-intervention group (n = 24). For each patient, we calculated the time from diagnosis to first treatment (surgery, systemic therapy, or radiation). Secondary measures included treatment-specific trends and the proportion of patients experiencing prolonged delays (>90 days). Results: Following MDR implementation, the median time from diagnosis to treatment decreased by 6 days, representing an approximately 11% relative reduction. The proportion of patients experiencing prolonged delays (>90 days) decreased from 20% pre-intervention to 13% post-intervention. Treatment timelines became more consistent after MDR implementation, as reflected by a narrower interquartile range. The greatest improvement was observed among patients initiating systemic therapy, while surgical timelines showed modest improvement and radiation timelines remained generally stable. In both periods, the longest delays were primarily associated with cases requiring external referral. Conclusions: Weekly multidisciplinary rounds improved coordination and contributed to more timely and reliable lung cancer treatment at our VA. The intervention lowered the median time to treatment, reduced the proportion of extended delays, and produced the most notable improvement among patients starting systemic therapy. Persistent longer delays were largely related to surgical planning and external referrals, highlighting areas for future workflow improvement. MDR represents a practical, low-resource strategy to enhance lung cancer care delivery for Veterans.
Enhancing cause-of-death attribution through real-world data integration: A framework to improve cancer mortality identification.
e23418 Background: Precise cause of death (COD) is essential for pharmaceutical and healthcare research in evaluating treatment effectiveness, product safety, outcomes, and health-economic analyses. This is amplified in oncological diseases where death, comorbidities, and time from treatment are critical variables for research. However, numerous studies have demonstrated substantial inaccuracies in death certificates, including misclassification of underlying causes, incomplete documentation, and major errors occurring in approximately 10-40% of U.S. certificates driven by limited clinical context and difficulty classifying multimorbid patients - which further undermine COD accuracy. Autopsy-based studies show discordance between recorded and actual causes of death, showing the need for more precision in identify cancer mortality. However, death certificates remain indispensable for mortality surveillance and public health decision-making, necessitating improved approaches in augmenting COD data. These issues are especially impactful in oncology, where misclassification of cancer-related deaths can distort mortality patterns, limit evaluation of treatment effectiveness, and obscure disparities. Methods: The Veritas COD solution was developed utilizing a real-world-data (RWD) model incorporating up-to three years of longitudinal claims, diagnoses, procedures, and Unified Medical Language System (UMLS) concept mapping. This framework creates standardized, contextualized COD profiles that bridge aggregate reporting (e.g., CDC) and ad-hoc data sources. By using UMLS concept mapping as a bridging tool, the solution can draw together multiple disparate sources and calculate likely cause of death and comorbidity information. To evaluate its impact, privacy-preserving record linkage (PPRL) was applied to combine Connecticut death records with Veritas calculated COD values. Cancer-related mortality values sourced from: (1) state-reported COD alone versus (2) enhancement of state-reported data by Veritas COD. Results: Integration of Veritas COD profiles with state mortality data produced a 33% increase in the number of decedents showing cancer as an underlying COD compared with state reporting alone. Newly attributed cases often involved individuals with multimorbidity or ambiguous certificate entries - categories known to exhibit high misclassification rates in research. This demonstrates the model's ability to recover cancer-related deaths overlooked in traditional reporting systems. Conclusions: Using an RWD-anchored COD solution addresses key weaknesses of death certificate-only systems and substantially improves cancer COD ascertainment. This framework supports more accurate epidemiologic insights, strengthens oncology outcomes research, and offers a scalable foundation for enhanced mortality surveillance.
Association of survival with clinical characteristics and CD68/CD206 expression in stage IIIA squamous cell lung carcinoma.
e20027 Background: Stage IIIA squamous cell lung carcinoma (SqCLC) has a poor prognosis, with 5-year survival rarely exceeding 30-35% even after radical treatment. The tumor microenvironment, particularly tumor-associated macrophages (TAMs), plays a key role in non-small cell lung cancer biology. This study aimed to evaluate the association between overall survival (OS) in stage IIIA SqCLC and clinical factors along with the expression of CD68 (pan-macrophage marker) and CD206 (M2-like macrophage marker) in tumor stroma and parenchyma. Methods: The study included 31 patients with stage IIIA SqCLC. Based on the median OS (42 months), patients were divided into short-survivors (OS < 42 months, n=20) and long-survivors (OS ≥ 42 months, n=11). Immunohistochemical staining was performed for CD68 (KP-1, Cell Marque) and CD206 (Orb94710, Biorbyt). The Mann-Whitney U test, Pearson's χ² test, and Spearman's correlation were used for statistical analysis. Results: High stromal CD68 expression was associated with better OS. The median stromal CD68 level was 1.4-fold higher in long-survivors (20 [IQR: 18.5-28.5]) compared to short-survivors (p=0.002). No significant survival differences were found for parenchymal CD68 or tumor CD206 expression. Adverse prognostic clinical factors included pneumonectomy (2.9 times more frequent in short-survivors, p=0.039) and the presence of comorbidities (2.8 times more frequent in short-survivors, p=0.001). Tumor size, nodal involvement, smoking status, and treatment regimens showed no significant differences. A significant negative correlation between stromal CD68 and parenchymal CD206 was found in long-survivors (ρ=-0.74, p<0.05), which was absent in the short-survivor group. Conclusions: The integration of clinical factors (pneumonectomy, comorbidities) with immunohistochemical markers, specifically high stromal CD68 expression and its inverse correlation with parenchymal CD206, may improve risk stratification and prognosis in patients with stage IIIA squamous cell lung carcinoma.
Enabling blood-based mass spectrometry MRD detection in multiple myeloma without archived serum samples.
7556 Background: Minimal residual disease (MRD) assessment in multiple myeloma (MM) relies almost exclusively on bone marrow (BM) biopsy, an invasive, costly, and spatially limited procedure that is poorly suited for frequent longitudinal monitoring and may miss focal or extramedullary disease. Blood-based MRD strategies offer a less invasive, lower-cost alternative that could enable more frequent surveillance and earlier detection of disease progression. Mass spectrometry (MS)-based detection of monoclonal immunoglobulin peptides in peripheral blood is a promising MRD approach; however, current methods typically require prior identification of circulating M-protein amino acid sequences from archived serum, limiting applicability in patients without banked samples. We sought to determine whether patient-specific immunoglobulin V(D)J sequences could be reconstructed from BM-derived DNA or RNA, or from peripheral blood RNA, to enable blood-based MRD detection. Methods: We analyzed RNA-seq and whole exome sequencing (WES) from BM plasma cells and RNA-seq from peripheral blood mononuclear cells in 75 patients with MM, all of whom had abnormal plasma cells identified by flow cytometry. Immunoglobulin heavy chain (IGH) V(D)J sequences were reconstructed using MiXCR, and the dominant productive clonotype in the BM was selected per patient. Variable-region sequences containing complementarity-determining region 3 (CDR3) and adjacent framework regions were extracted when available. Peripheral blood RNA-seq was evaluated for clonotype recovery without BM sampling. In silico proteolytic digestion was performed to identify peptides compatible with standard MS detection. Results: Across 75 patients, dominant IGH clonotypes were reconstructed from 100% of BM sequencing data. From these clonotypes, a mean of 7 RNA-seq–derived peptides and 6 WES-derived peptides per patient were identified, with a mean of 2 peptides shared between platforms. Fifty patients (67%) generated ≥10 MS-compatible peptides, and 33 patients (44%) had at least one peptide shared between RNA-seq and WES. Among 51 patients with paired tumor and peripheral blood RNA-seq, dominant clonotypes were detectable in peripheral blood by CDR3 matching in 30 patients (58.8%). Conclusions: Patient-specific immunoglobulin clonotypes can be reliably reconstructed from prior BM sequencing data, yielding MS-compatible peptide targets for downstream analysis. In selected patients, clonotype discovery is feasible directly from peripheral blood, potentially reducing the need for invasive BM sampling. This approach overcomes a key limitation of existing MS-based MRD assays by enabling peptide target discovery in patients without archived serum but with available BM sequencing. Additional studies are required to validate MS detection of these peptides and establish a scalable, minimally invasive blood-based MRD platform.
Scaling digital patient navigation to improve access to multidisciplinary melanoma care.
1528 Background: Multidisciplinary (multiD) melanoma care is associated with improved patient (pt) outcomes, yet access is variable due to geographic, informational, and system-level barriers. We previously reported preliminary single-center feasibility of engaging pts using a digital patient navigation platform (DPNP) that provides information about melanoma, cutaneous oncology subspecialists, and clinical trials. We now report results from a multi-site expansion evaluating engagement across academic (Johns Hopkins; JH) and regional health systems (RHS). Methods: In this IRB-approved study, adult pts recently diagnosed with melanoma at JH or at a participating RHS were identified monthly using ICD-10 codes. Pts who were not already receiving multiD melanoma care at JH were sent DPNP invitations via their electronic medical record (EMR)-based pt portal. The primary endpoint was clickthrough rate (CTR; % of eligible pts who clicked the link in the invitation), benchmarked against web-based healthcare messaging standards (7%); invitation of ≥183 pts per setting was targeted (one-sided 90% CI exceeding benchmark if CTR ≥7.5%). Secondary endpoints included conversion rate (registration after clickthrough; benchmark 10%) and subsequent pursuit of multiD melanoma care. Results: From Nov 2023 - Dec 2025, 194 eligible pts were identified at JH; from Dec 2024 - Dec 2025, 356 at RHS; all were sent DPNP invitations. CTR: 41% at JH (80/194, 95% CI 34.2%-48.5%), 30% at RHS (106/356, 95% CI 25.1%-34.8%). Conversion rates were 23% (18/80, 95% CI 13.9%-33.2%) and 25% (27/106, 95% CI 17.5%-34.9%), respectively. Of 45 total registrants, 42 (93%) provided demographic data: mean age 59.7 yrs (range 25-83), 55% female, melanoma stage 0-IV. Among 16 JH and 26 RHS registrants, 2 (13%) and 6 (23%), respectively, had high-risk (stage ≥II) melanoma warranting a multiD consultation. After registering, 2/2 (100%) and 0/6 (0%) high-risk pts sought multiD care. Median distance to JH was 45 miles and 100 miles for JH and RHS registrants, respectively. Conclusions: In this multi-site study, melanoma pt engagement with a DPNP significantly exceeded established benchmarks across academic and RHS, demonstrating scalability of EMR-integrated outreach. However, among pts with high-risk melanoma, transition to multiD care occurred more frequently at the academic center than in RHS, revealing setting-specific barriers to converting engagement into subspecialty care. These findings indicate that while digital navigation can effectively identify unmet need across care environments, patient-initiated pathways alone may be insufficient to close access gaps. In response, we are developing a clinician-facing platform designed to overcome informational and geographic barriers by enabling collaboration between community clinicians and multiD oncology teams, thereby facilitating delivery of subspecialty cancer care closer to home.