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Tumour-infiltrating lymphocyte (TIL) therapy has emerged as a promising adoptive cell transfer strategy for solid tumours. The recent accelerated approval of lifileucel by the Food and Drug Administration marks a significant milestone in the clinical application of TIL therapy. This review comprehensively examines the historical development, biology, clinical efficacy, safety and limitations of TIL therapy. We explore advancements in TIL manufacturing, including novel culture techniques, genetic modifications and automation, to enhance scalability and effectiveness. Despite promising results, TIL therapy faces challenges such as high-dose interleukin-2 toxicity, complex manufacturing processes and immune evasion mechanisms. Emerging strategies, including checkpoint inhibitor combinations, engineered TIL constructs and metabolic reprogramming, aim to improve TIL therapeutic efficacy. This review provides insights into the evolving landscape of TIL therapy and its potential to enhance current cancer immunotherapy.

9503 Background: Neoadjuvant ± adjuvant immunotherapy improves event-free survival relative to adjuvant immunotherapy alone for patients with high-risk resectable stage III melanoma. However, the optimal regimen balancing efficacy and tolerability is not known. T-cell immunoglobulin and ITIM domain (TIGIT) is a promising immune checkpoint but its therapeutic potential in stage III melanoma is underexplored. Methods: In this phase II trial, patients with resectable, macroscopic stage III melanoma received four 21-day neoadjuvant cycles of 1200mg IV atezolizumab (atezo, anti-PD-L1) + 600mg IV tiragolumab (tira, anti-TIGIT), followed by therapeutic lymph node dissection (TLND) and eight 21-day adjuvant cycles of 1200mg IV atezo. Primary endpoints were pathologic response (of all patients initiating neoadjuvant therapy) and recurrence-free survival (RFS) from the time of TLND in patients who were operated on per protocol and received adjuvant therapy. Secondary endpoint was adverse events (AEs); exploratory endpoints included event-free survival (EFS) and distant metastasis-free survival (DMFS). Results: Thirty-four patients, median age 59 years, were accrued and initiated neoadjuvant atezo/tira. 76.5% had >1 metastatic lymph node involved at baseline and 73.5% presented with Stage IIIC disease. All 34 patients were evaluable for AEs, pathologic response and EFS. Four patients were diagnosed with metastatic disease during neoadjuvant treatment, while 30 had TLND per protocol and 28 received adjuvant treatment and were evaluable for RFS and DMFS. Major pathologic responses (MPR, ≤10% viable tumor) were observed in 16/34 patients (47.1%, Table). With 19.9 months median follow-up from registration, 12-month EFS was 72.0% (95% CI 57.9 to 89.5%). With 16 months median follow-up from operation, 12-month RFS was 73.3% (n=28, 95% CI 56.9 to 94.5%), while 12-month DMFS was 86.0% (n=28, 95% CI 72.2 to 100%). In the 16 patients with an MPR, 2 did not receive adjuvant treatment and were followed for 33.3 and 10.8 months without recurrence/death. In the remaining 14 patients, 12-month RFS and 12-month DMFS were both 91.7% (95% CI 77.3 to 100%). 5 patients (14.7%) experienced any grade 3+ AE with 2 (5.9%) at least possibly related to the neoadjuvant regimen. Conclusions: Among patients with high-risk resectable stage III melanoma, neoadjuvant atezo/tira was a promising regimen with a favorable safety profile and warrants further study. Identification of predictive biomarkers will allow for optimization of neoadjuvant therapy for individual patients. Clinical trial information: NCT03554083 . Pathologic response. N=34 Major Pathologic Response 16 (47.1%) Pathologic complete response (no viable tumor) 13 (38.2%) Near-pathologic complete response (0.1−10% viable tumor) 3 (8.8%) Pathologic partial response (>10.0−50% viable tumor) 2 (5.9%) Pathologic non-response (>50% viable tumor) 12 (35.3%) No per protocol operation 4 (11.8%)

Melanoma is the deadliest form of skin cancer. The median age at diagnosis is 66. While most patients are treated with immunotherapy, the use of targeted therapy is a valid alternative for patients whose tumors harbor a BRAF or c-KIT driver mutation. These agents, while effective, come with a variety of side effects which limit their use, especially in older patients. We sought to assess the efficacy and toxicity of these agents in older melanoma patients. Melanoma patients over 65 treated with BRAF/MEK or c-KIT inhibitors were retrospectively identified, and their data were analyzed for treatment efficacy and toxicity. All data were compared using the Chi-square test for categorical comparisons and the Kruskal–Wallis method for median comparisons. One hundred and sixteen patients were identified. One hundred and six patients were treated with BRAF/MEK inhibitors. The assessed response rate (RR) was 83% and was comparable across different subgroups, including advanced line patients and those with a more aggressive disease. The median progression free survival (PFS) was 7.9 months, and the median overall survival (OS) was 15.7 months. Twenty-seven percent experienced grade 3–4 toxicity leading to a 24% treatment discontinuation rate. Another 10 patients were treated with the c-KIT inhibitor imatinib, for whom the assessed RR was 55%. The median PFS was 4.3 months, and the median OS was 22.6 months. Forty percent needed dose reductions, yet none had to stop treatment due to adverse effects. The use of targeted therapy in older patients is effective yet challenging due to toxicity. Deploying mitigation strategies can help maximizing their usefulness.

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients > 65). The use of BRAF & MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients > 65. Methods: We identified electronic medical records of all melanoma patients > 65 that were treated with BRAF & MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second & third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF & MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.

AbstractIntroductionStructured data capture requires defined languages such as minimal Common Oncology Data Elements (mCODE). This pilot assessed the feasibility of capturing 5 mCODE categories (stage, disease status, performance status (PS), intent of therapy and intent to change therapy).MethodsA tool (SmartPhrase) using existing and custom structured data elements was Built to capture 4 data categories (disease status, PS, intent of therapy and intent to change therapy) typically documented as free‐text within notes. Existing functionality for stage was supported by the Build. Participant survey data, presence of data (per encounter), and time in chart were collected prior to go‐live and repeat timepoints. The anticipated outcome was capture of >50% sustained over time without undue burden.ResultsPre‐intervention (5‐weeks before go‐live), participants had 1390 encounters (1207 patients). The median percent capture across all participants was 32% for stage; no structured data was available for other categories pre‐intervention. During a 6‐month pilot with 14 participants across three sites, 4995 encounters (3071 patients) occurred. The median percent capture across all participants and all post‐intervention months increased to 64% for stage and 81%–82% for the other data categories post‐intervention. No increase in participant time in chart was noted. Participants reported that data were meaningful to capture.ConclusionsStructured data can be captured (1) in real‐time, (2) sustained over time without (3) undue provider burden using note‐based tools. Our system is expanding the pilot, with integration of these data into clinical decision support, practice dashboards and potential for clinical trial matching.

Abstract Background:Racial disparities in multiple myeloma (MM) outcomes are well established. Clinical characteristics and cytogenetic abnormalities dictate outcomes in MM but historically they have been mostly defined in White patients with paucity of information regarding racial-ethnic minorities. Hispanics are the fastest growing racial-ethnic subgroup in United States and have the worst overall survival (OS) in MM but differences in disease presentation among Hispanics compared to Whites, the historical control, are undefined. Methods: MM patients seen at Mayo Clinic in Florida (MCF) and Arizona (MCA) between 1/1/2000-06/15/2017 were included. Patient and disease characteristics including gender, age at diagnosis, bone marrow (BM) plasmacytosis, laboratory data [M spike, creatinine (Cr), beta-2-microglobulin (B2M), Hemoglobin (Hb), calcium (Ca)], MM subtype [IgG, IgA, light chain (LC), other], LC subtype (κ, λ, biclonal), presence of lytic bone lesions, disease stage (DS, ISS, R-ISS), mSMRT cytogenetic risk category, presence of individual cytogenetic mutations (deletions, translocations, gains, trisomy/hyperdiploidy) was collected. Comparisons between Hispanic study cohort characteristics and historical control were made by Chi-square, Fischer's exact and Signed rank tests, where applicable, using data from previous publications [Kyle et al, 2003 (n=1027) and Fonseca et al, 2003 (n=351)]. Patients with missing data on a certain clinical or disease feature were not included in the statistical analysis of that specific characteristic. Results: A total of 1705 MM patients were screened and 266 Hispanic patients seen at either site between the specified dates were identified for the analysis. These included equal number of males and females (n=133 each) with a median age of 58 years (range 25-87). IgG disease was seen in 52% with IgA and LC subtypes in 23% each. LC subtype was κ in 67%, λ in 31% and biclonal in 2% cases. Lytic and extramedullary disease were noted in 71% and 44% patients, respectively. DS and R-ISS stage at the time of MM diagnosis was not available in most patients while ISS stage among 150 patients showed stage 1, 2 and 3 in 48%, 28% and 24% patients, respectively. mSMART risk categories were present in 226 patients and included high, intermediate and standard risk in 12%, 11% and 77% patients, respectively. Of these 226 patients, cytogenetic disease prior to starting any MM treatment was available in 153 patients with similar risk category distribution. Median follow up for the whole Hispanic cohort was 38.6 months with a median OS 10.7 years (Figure 1). Comparison with historical control datasets which were 97% or greater comprised of White patients showed some significant differences for the Hispanic cohort including gender distribution, median age, BM plasmacytosis at the time of diagnosis, median Hb, Cr or M spike at presentation, light chain subtype, presence of lytic bone disease and certain cytogenetic alterations including t(4;14) and del13q/monosomy (Table 1). We did not note differences in high-risk cytogenetics between Hispanics and historical White controls. Conclusions: We report the first description of clinical and cytogenetic characteristics of Hispanic MM patients. The current and historical datasets that we have used are all from Mayo Clinic experience, thus making reasonable comparisons possible. We were able to confirm previous reports of demographic differences in Hispanics e.g., younger age at diagnosis. While some characteristics were significantly different, the clinical and cytogenetic differences we note do not clearly explain the inferior OS noted for Hispanics in population-based studies. Significant differences that we report warrant continued exploration in larger institutional and public databases in addition to a continued look into healthcare access and utilization. An ongoing collaborative analysis with data from Mayo Clinic, University of Miami and University of Southern California, Los Angeles is ongoing. Disclosures Fonseca: AMGEN: Consultancy; Jansen: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Celgene Corporation: Consultancy, Research Funding; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy; Novartis: Consultancy. Kelly: Pharmacyclics: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Jannsen: Honoraria. Sher: LAM Therapeutics, Inc: Research Funding. Ailawadhi: Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

230 Background: Inpatient mortality review is commonly used to improve patient care. Individual review of outpatient deaths is less common, yet 30-day mortality after hospital stay is an important quality metric. In this study, we sought to identify opportunities for care improvement by reviewing outpatient mortalities for cancer patients who died within 30 days of hospitalization. Methods: We identified 48 patients at Mayo Clinic Florida, with a hematologic (heme) or solid tumor (onc) cancer, who died within 30 days of an index hospital stay in 2018. We created a 32-question review survey to address quality of care around the hospital stay. The review team consisted of 1) heme or onc attendings, 2) heme/onc fellows, and 3) palliative care attendings. Each case was reviewed by one member of each of the 3 groups, split into heme or onc cases. Discrepancies in objective data points were resolved by the research team. Results: Of 143 surveys sent to 13 physicians (3 heme), 112 responses from 11 physicians (1 heme) for 47 patients were received. Twenty-one patients (45%) received cancer therapy within 30 days of death, and 23 (49%) were admitted >2 times in 2 months prior to death. For onc cases, attendings rated prognosis as discussed 83% of the time, vs 65% of fellows and 39% of palliative care; in heme cases, the attending rated prognosis as discussed 11% of the time, vs 86% of fellows and 50% of palliative care. In heme cases, the attending rated expected survival <3 months in 33% of cases vs 71% by fellows and 89% by palliative care; in onc cases, the reviews were more consistent (79% attending, 85% fellow, 93% palliative care). See Table for timing of prognosis discussions and palliative care involvement. Conclusions: The most common improvement opportunities identified by reviewing heme/onc patients who died within 30 days of a hospital stay included documented prognosis discussion and involvement of palliative care. Opportunities differed between heme and onc patients. Future directions include identifying and mitigating barriers that providers face in reaching these goals for their patients. [Table: see text]

e21069 Background: Lobectomy remains the standard of care for definitive management of stage I non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is considered primarily for patients who were either unwilling to have surgery or deemed to be medically unfit for surgery. Current NCCN guidelines indicate the use of CT for surveillance following curative-intent therapies and recommend CT every 6 months for 2-3 years followed by CT annually without clear guidance on how long to keep doing annual CT scans. This study aims to evaluate the patterns of lung cancer recurrence within and beyond five years post curative therapy. Methods: Patients diagnosed with stage I NSCLC and treated with either curative surgery or SBRT from 1998-2016 at Mayo Clinic Florida were identified. Through retrospective chart review, data was collected on clinical and demographic features, surveillance imaging, pathology, time to recurrence or new primary lung cancer, and location of recurrence (loco-regional vs. distant). Statistical analysis with chi-square test was performed to identify risk factors associated with recurrence. Results: In total, 203 patients with stage I NSCLC were identified with most patients treated with surgery (n = 181) compared with SBRT (n = 22). Median time of follow up is 85 months. Overall, 48 patients (23.6%) developed a recurrence, with the median time to recurrence of 22.3 (3.9-69.8) months. Most recurrences were identified within 5 years from curative therapy (42/48) with 6 patients having a recurrence between 5 and 10 years post curative therapy. Of the 37 patients followed for more than 10 years, there were no recurrences. Twenty seven patients had new primary lung cancers identified and among them, 15 were found within 5 years, 10 found between 5-10 years and 2 found beyond 10 years. Median time to new primary lung cancer was 58.1 months. A positive smoking history and stage IB were found significantly associated with lung cancer recurrence (chi-square test P = 0.007 and P = 0.04 respectively), while age, gender, histology, grade, and treatment type had no association. Conclusions: In this study of 203 patients with stage I NSCLC treated with curative intention, there was no evidence of recurrent disease after 10 years following curative therapy, questioning the utility of continued annual CT surveillance once patients hit this milestone.