Castle Biosciences Research Articles

Commercial Diagnostics and Emerging Precision Medicine Technologies in Psoriasis and Atopic Dermatitis.

While psoriasis and atopic dermatitis (AD) are two common dermatological conditions, their diagnosis and therapeutic decision-making pathways are often complex. As a result, there has been increased focus on the development of precision medicine approaches for psoriasis and AD. Two companies at the forefront of dermatology precision medicine research are Mindera Health and Castle Biosciences. Here, we review the technologies developed by these two companies using a dermal diagnostic patch and superficial skin scrapings, respectively, their research published to date, and their future research goals. Research from both companies shows promise in predicting the response of inflammatory skin disease to biologics using minimally invasive techniques. However, challenges to adoption include insurance coverage and patient trust in the technologies. While there are several differences between Mindera Health and Castle Biosciences, they have a shared goal of utilizing minimally invasive technologies to sample skin and predict response to biologic treatments using a panel of optimized biomarkers.

TEMPORARY REMOVAL: Limitations of the Commercially Available Gene Expression Test in Predicting Cutaneous Squamous Cell Carcinoma Metastasis and Clinical Outcomes

BackgroundClinical genetic tests are integral to healthcare decision-making. However, the unclear regulatory framework, especially regarding products that evade stringent FDA oversight, may compromise test validity and transparency. ObjectiveTo critically evaluate the DecisionDx® cutaneous squamous cell carcinoma test by Castle Biosciences for its dataset biases, gene panel selection, and reported accuracy metrics, providing insight into broader challenges in the clinical genetic testing landscape. MethodsIndependent analyses of the DecisionDx®-SCC 40-GEP test data from Castle Biosciences were conducted. These included comparisons to clinical genetic testing standards, analysis of prevalence metrics against national cSCC rates, gene ontology of 34 genes for cSCC associations, and evaluation of accuracy metrics. ResultsThe DecisionDx®-SCC met 11 of 44 CDC’s ACCE criteria for clinical genetic testing. Its dataset showed a metastasis prevalence higher than the national average. Out of 34 genes, 15 had known associations with cSCC. Inconsistencies in accuracy metrics presentation were noted, particularly in moderate and high-risk stratifications. ConclusionAnalysis of DecisionDx®-SCC indicates potential biases and ambiguities, exacerbated by differences between FDA and CLIA standards. This highlights the need for systematic validation and a unified regulatory approach, stressing the necessity for precise and dependable genetic testing in patient care.

Impact of gene expression profiling on diagnosis and survival after metastasis in patients with uveal melanoma.

Surveillance frequency for metastasis is guided by gene expression profiling (GEP). This study evaluated the effect of GEP on time to diagnosis of metastasis, subsequent treatment and survival. A retrospective study was conducted of 110 uveal melanoma patients with GEP (DecisionDx-UM, Castle Biosciences, Friendswood, Texas, USA) and 110 American Joint Committee on Cancer-matched controls. Surveillance testing and treatment for metastasis were compared between the two groups and by GEP class. Rates of metastasis, overall survival and melanoma-related mortality were calculated using Kaplan-Meier estimates. Baseline characteristics and follow-up time were balanced in the two groups. Patients' GEP classification was 1A in 41%, 1B in 25.5% and 2 in 33.6%. Metastasis was diagnosed in 26.4% ( n = 29) in the GEP group and 23.6% ( n = 26) in the no GEP group ( P = 0.75). Median time to metastasis was 30.5 and 22.3 months in the GEP and no GEP groups, respectively ( P = 0.44). Median months to metastasis were 34.7, 75.8 and 26.1 in class 1A, 1B and 2 patients, respectively ( P = 0.28). Disease-specific 5-year survival rates were 89.4% [95% confidence interval (CI): 81.0-94.2%] and 84.1% (95% CI: 74.9-90.1%) in the GEP and no GEP groups respectively ( P = 0.49). Median time to death from metastasis was 10.1 months in the GEP group and 8.5 months in the no GEP group ( P = 0.40). There were no significant differences in time to metastasis diagnosis and survival outcomes in patients with and without GEP. To realize the full benefit of GEP, more sensitive techniques for detection of metastasis and adjuvant therapies are required.

Diagnostic Discordance Among Histopathological Reviewers for Difficult-to-Diagnose Melanocytic Lesions

Purpose: Histopathological examination is adequate for most melanocytic neoplasms. However, there is a subset of lesions with uncertain malignant potential that are difficult-to-diagnose where utilization of ancillary tests may be considered to aid in providing a more definitive diagnosis.
 Study design: Under an IRB-approved protocol, 3,317 melanocytic lesions underwent independent diagnostic review by up to 9 unique board-certified dermatopathologists. Each lesion received ≥ 3 diagnoses via electronic whole slide images with zoom-in capability as benign, malignant, or unknown malignant potential (UMP). Lesions were subsequently binned according to the results of dermatopathology review in the following manner: concordant (all diagnoses of the same designation); conflicting (both benign and malignant designations); majority (a single designation with the highest number of diagnoses); and equivocal (equal number of different designations). Here we describe the identification of lesions suitable for ancillary testing.
 Results: 30% of lesions were concordant benign and 46.3% were concordant malignant, indicating 76.3% of all lesions were not difficult-to-diagnose. 23.7% of lesions had some level of diagnostic difficulty and/or ambiguity defined by disagreement between reviewers and would be suitable for ancillary testing. Within these ~24%, 7.3% of lesions were majority benign, 4.8% of lesions were majority malignant, 2.7% were majority UMP, 6.9% of lesions were conflicting, and 1.6% of lesions were equivocal.
 
 Conclusions: We demonstrate that in a large cohort of suspicious pigmented lesions, ~24% were difficult-to-diagnose, supporting the need for additional objective diagnostic tools. Patient care would benefit from ancillary testing to aid the diagnosing pathologist in identification of the most appropriate diagnosis to optimize patient management.
 Potential conflicts of interest: This study was supported by Castle Biosciences, Inc. GAH and JAP have served as consultants for Castle Biosciences, Inc. MSG is an employee shareholder of Castle Biosciences, Inc. SIE is a consultant and shareholder for Castle Biosciences, Inc. Editorial assistance was provided by Brooke H. Russell, PhD, and Jason H Rogers, MSc, both employee shareholders of Castle Biosciences, Inc.

Patients with Atopic Dermatitis Not on Systemic Therapy have High Rates of Severe, Uncontrolled Disease, and Considerable Impact on Quality of Life

Patients with Atopic Dermatitis Not on Systemic Therapy have High Rates of Severe, Uncontrolled Disease, and Considerable Impact on Quality of Life

Relationship of Histopathologic Parameters and Gene Expression Profiling in Malignant Melanoma.

Histopathologic characteristics (HC) are a mainstay in melanoma prognosis; gene expression profiling (GEP) has emerged as a potential additional independent value. To elucidate HC predictive of groups obtained via GEP of malignant melanoma. A retrospective study analyzing HC of 265 melanomas submitted for GEP over the course of 8years. GEP was conducted as a part of regular clinicopathologic workup through Castle Biosciences Decision Dx®. Of the 265 cases, the major HC found to have an association with reported gene expression profiles were melanoma histology subtype, depth of invasion, and presence of ulcer. This study is limited by its cross-sectional nature. Causation and long-term related outcomes of the use of GEP versus American Joint Committee on Cancer histopathologic staging cannot be ascertained by this design. An association, but no definitive prediction, exists between histopathologic categories of depth of invasion, melanoma subtype, and presence or absence of ulcer and gene expression profiles. GEP adds valuable data to the evaluation of malignant melanomas that cannot be definitively predicted by conventional models. The findings add to needed groundwork for comparison of traditional markers and molecular genotyping and begins to build a robust predictive model for better outcomes in patients with malignant melanoma.

Integrating the 31-gene expression profile test into clinical decision-making to guide risk-aligned care decisions for patients with stage I-III cutaneous melanoma: NCI-SEER Analysis.

6601 Background: Cutaneous melanoma (CM) management depends on an estimate of recurrence risk or death. Because of recognized disease risk and drug efficacy, pembrolizumab immunotherapy has been approved for stage IIB-C patients. However, it is a treatment with potential financial and biological toxicities with 16% of patients experiencing severe treatment related adverse events. Improved risk stratification could identify individuals for whom more selective management would be appropriate. In collaboration with the NCI Surveillance, Epidemiology, and End Results (SEER) program, which includes information on patients tested with a 31-gene expression profile (31-GEP) test in an unbiased and unselected manner, we confirm the 31-GEP adds independent prognostic value in patients with stage I-III CM, and investigated whether the 31-GEP could identify stage IIB-C patients who might reasonably avoid adjuvant therapy while also identifying patients with stage I disease who might benefit from more aggressive diagnostic and/or therapeutic intervention. Methods: SEER registries linked CM cases diagnosed 2013-2018 to 31-GEP test results provided by Castle Biosciences (9,207 matched) using a registry trusted third party (honest broker), including subsets of stage IIB-IIC (n=775) and stage I (n=5,651) melanoma. The primary endpoint was melanoma-specific survival (MSS). The 31-GEP risk-groups included Class 1A (low), Classes 1B/2A (intermediate), and Class 2B (high). Each was compared using Kaplan-Meier analysis and the log-rank test. Results: In the overall cohort, patients with a Class 1A result had a significantly higher 5-year MSS than a Class 1B/2A or Class 2B result (97.4% vs. 93.5% vs. 83.3%, p<0.001). In multivariable analysis, a Class 2B result (HR=3.26, p<0.001) and positive lymph node status (HR=3.41, p<0.001) were the strongest predictors of diminished MSS. In stage IIB-C, 18.8% (146/775) of patients received a Class 1A result with an associated 5-year MSS of 89.1% (vs. Class 2B: 76.6%, p=0.001), despite the absence of pembrolizumab approval for the evaluated SEER population. Alternatively, 4.6% (260/5,651) of patients with stage I disease had a Class 2B result, with an associated 5-year MSS of 92.3% (vs. Class 1A: 98.0%, p<0.001). Conclusions: The SEER database allowed a non-biased analysis of a large cohort of patients with stage I-III CM who were tested with the 31-GEP. The 31-GEP identifies patients, including those with stage IIB-C disease, with favorable outcomes and could help physicians and patients decide whether to pursue adjuvant therapy. Moreover, the 31-GEP identities high-risk patients, including those with stage I disease, for whom more aggressive follow-up and early intervention should be considered.

Long-term outcomes in a population-based cohort of 2,967 uveal melanoma patients clinically tested with the 15-gene expression profile: A collaborative study with the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program Registries.

e21574 Background: Metastatic risk prediction in uveal melanoma is commonly performed using a commercially available 15-gene expression profile (15-GEP) test. A recent collaborative effort with the NCI’s SEER program registries allowed for serial linkage of UM patients captured by SEER registries with clinical 15-GEP test results. The objective of this study was to confirm the 15-GEP test’s performance in clinically tested uveal melanoma patients with long-term outcomes at the population level. Methods: Following established operating procedures, SEER registries linked UM cases diagnosed from 2010–2019 to 15-GEP test results provided by Castle Biosciences using a trusted third-party (honest broker). The patients were clinically tested as recommended by guidelines (testing was performed either on fine needle aspiration biopsy tissue or formalin-fixed, paraffin-embedded tissue from enucleations). De-identified data were provided to NCI and Castle Biosciences scientists for this study. Kaplan-Meier analysis with log-rank test was used to evaluate the available endpoints of melanoma-specific survival (MSS) and overall survival (OS). Multivariable analysis was performed with Cox proportional hazards modeling. Results: A total of 2,967 UM patients ≥ 18 years of age with localized disease (excluding Stage IV) and 15-GEP test result were included in this study (Class 1, 1904; Class 2, 1063). The cohort was 51.7% male, with a median age of 63 years. Median follow-up time was 2.2 years. Patients with a low-risk (Class 1) vs. high-risk (Class 2) result had significantly higher 7-year survival outcomes (OS, 78.9 vs. 31.8%, p < 0.001; MSS, 90.4 vs. 41.6%, p < 0.001, respectively). Patients with a Class 2 result were over six times more likely to experience a UM-related death than those with a Class 1 result (31.8 [338/1063] vs. 5.0% [96/1904]; p < 0.001). Multivariable analysis showed that the 15-GEP was the strongest independent predictor of MSS when compared with clinicopathologic features (tumor diameter or thickness) and age, with a Class 2 hazard ratio of 6.2 (95% CI, 3.9–9.7; p < 0.001). Notably, there was no association between GEP class call distribution and socioeconomic status as measured by the Yost index (p = 0.79). Conclusions: In this analysis, the 15-GEP accurately stratified risk of death from UM in a clinically tested, population-based cohort of patients, confirming previous studies. Socioeconomic status did not impact the likelihood of getting a high-risk result, suggesting equitable access to care for patients who receive 15-GEP testing. Ongoing analyses of SEER-linked UM data will include patients who received a PRAME test result, allowing for assessment of this adjunctive biomarker in combination with the 15-GEP result.

Subtype performance of the ancillary diagnostic 23- and 35-gene expression profile (GEP) tests for difficult-to-diagnose melanocytic lesions

Background: Histopathological examination is adequate for most melanocytic neoplasms; however, there is a subset of lesions that are difficult to diagnose. The 23- and 35-gene expression profile (GEP) tests deliver results of suggestive of benign neoplasm, suggestive of malignant neoplasm, or intermediate (cannot exclude malignancy). They are intended to provide clinicians with objective results to be interpreted in the context of clinical, laboratory, and histopathological features to achieve a definitive diagnosis. Both GEPs are stand-alone tests that are independently validated and clinically available. Greater than 99% benign or malignant reporting is achieved clinically when the 23-GEP test is processed first, and if an intermediate result or test failure occurs, the 35-GEP is utilized.
 Methods: The performance of the 23- and 35-GEP tests using this methodology was tested on unequivocal cases from a variety of subtypes (101 benign, 249 malignant). Lesions were included if 2/3 dermatopathologist diagnoses were concordant. Subtype designation was determined by the dermatopathologist that submitted the lesion for the study.
 Results: The overall accuracy metrics in this cohort were 96.0% sensitivity and 87.8% specificity. The results demonstrated 100% sensitivity in several melanoma subtypes including acral lentiginous (n=15), desmoplastic (n=20), melanoma in situ (n=16), and nevoid (n=16). Other melanoma subtypes showed sensitivity metrics of: lentigo maligna, 96.7% (n=31); nodular, 95.1% (n=81); superficial spreading, 97.7% (n=42); and spitzoid, 85.0% (n=20). Subtypes of benign nevi showed a specificity of: blue, 96.7% (n=30); compound, 85.7% (n=42); junctional, 77.8% (n=18); and Spitz, 100% (n=7).
 Conclusions: Overall, we demonstrate that use of the 23- and 35-GEP diagnostic test workflow results in high accuracy across many subtypes of benign and malignant melanocytic neoplasms.
 Financial Disclosures: JAP has served as a consultant for Castle Biosciences, Inc. SIE is a consultant and shareholder of Castle Biosciences, Inc. BHR, JJS, JHR, JKW, SJK, and MSG are employee shareholders of Castle Biosciences, Inc. KM has served as a consultant and investigator for studies supported by Castle Biosciences, Inc. This study was supported by Castle Biosciences, Inc.

P186 Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis

P186 Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis

E088 Safety of guselkumab in patients with psoriatic disease: an integrated analysis of 11 Phase 2 and 3 clinical studies in psoriasis and psoriatic arthritis

Abstract Background/Aims Guselkumab is a monoclonal antibody approved to treat moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). In this analysis, safety data from 11 Phase 2/3 studies of guselkumab were pooled to evaluate guselkumab safety in a large population of patients with psoriatic disease. Methods Guselkumab was generally administered as 100-mg injections at Week (W)0, W4, then Q8W in 7 psoriasis studies and at W0, W4, then Q4W or Q8W in 4 PsA studies. Patients randomized to placebo crossed over to guselkumab Q8W at W16 in 5 PsO studies and to guselkumab Q4W or Q8W at W24 in all PsA studies. Safety data were summarized for the placebo-controlled period (W0-W16 in PsO; W0-W24 in PsA) and through the end of the reporting period (up to 5 years in PsO; up to 2 years in PsA). Incidence rates of key safety events were integrated post-hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PY). Results During the placebo-controlled periods, 1061 patients received placebo (395 PY) and 2257 received guselkumab (856 PY). Through the long-term reporting periods, 4399 guselkumab-treated patients (PsO: 2891; PsA: 1508) contributed 10787 PY of follow-up (PsO: 8662 PY; PsA: 2125 PY). In PsO and PsA studies, pooled incidence rates of overall adverse events (AEs) were similar between guselkumab- and placebo-treated patients. Rates of serious AEs, AEs leading to discontinuation, serious infections, malignancy, and major adverse cardiovascular events were low and generally similar between guselkumab- and placebo-treated patients. Rates of safety events remained consistent through the long-term reporting period for guselkumab-treated patients (Table). No cases of Crohn’s disease or ulcerative colitis were reported in guselkumab-treated patients. No serum sickness-like or anaphylactic reactions related to guselkumab were reported. No opportunistic infections were reported in any guselkumab-treated PsO patient. Three cases of opportunistic infection were reported in pooled PsA studies (0.14/100 PY; all post-W52 in DISCOVER-2). No cases of active tuberculosis were reported across all studies. Conclusion In the most comprehensive analysis of guselkumab safety to date, AE rates in guselkumab-treated patients were similar to those observed with placebo and were stable throughout long-term follow-up. Disclosure B. Strober: Grants/research support; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Eli Lilly, Meiji Seika Pharma, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Dermira, Leo Pharma, Inc, Arcutis, Are. L. Coates: Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB; grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Jan. J. Yu: Shareholder/stock ownership; Janssen Research & Development, LLC, Johnson & Johnson. K. Rowland: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. E. Leibowitz: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. M. Miller: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. A. Kollmeier: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Li: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. Y. Wang: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. D. Chan: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Chakravarty: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; Y. Yang, Janssen Pharmaceutical Companies, Johnson & Johnson. Y. Yang: Shareholder/stock ownership; Janssen Pharmaceutical Companies, Johnson & Johnson. M. Shawi: Shareholder/stock ownership; Janssen Pharmaceutical Companies of Johnson and Johnson. M. Lebwohl: Grants/research support; Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy's Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Cor. P. Rahman: Shareholder/stock ownership; Janssen, Novartis, AbbVie, Eli Lilly and Company, Pfizer.

The impact of stage-related features in melanoma recurrence prediction: A machine learning approach

The impact of stage-related features in melanoma recurrence prediction: A machine learning approach

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

A retrospective analysis of the impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma

A retrospective analysis of the impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma

Expert Consensus on the Use of Prognostic Gene Expression Profiling Tests for the Management of Cutaneous Melanoma: Consensus from the Skin Cancer Prevention Working Group.

BackgroundPrognostic assessment of cutaneous melanoma relies on historical, clinicopathological, and phenotypic risk factors according to American Joint Committee on Cancer(AJCC) and National Comprehensive Cancer Network (NCCN) guidelines but may not account for a patient’s individual additional genetic risk factors.ObjectiveTo review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma.MethodsA literature search was conducted for original, English-language studies or meta-analyses published between 2010 and 2021 on commercially available GEP tests in cutaneous melanoma prognosis, clinical decision-making regarding sentinel lymph node biopsy, and real-world efficacy. After the literature review, the Skin Cancer Prevention Working Group, an expert panel of dermatologists with specialized training in melanoma and non-melanoma skin cancer diagnosis and management, utilized a modified Delphi technique to develop consensus statements regarding prognostic gene expression profile tests. Statements were only adopted with a supermajority vote of > 80%.ResultsThe initial search identified 1064 studies/meta-analyses that met the search criteria. Of these, we included 21 original articles and meta-analyses that studied the 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.), five original articles that studied the 11-GEP test (Melagenix; NeraCare GmbH), and four original articles that studied the 8-GEP test with clinicopathological factors (Merlin; 8-GEP + CP; SkylineDx B.V.) in this review. Six statements received supermajority approval and were adopted by the panel.ConclusionGEP tests provide additional, reproducible information for dermatologists to consider within the larger framework of the eighth edition of the AJCC and NCCN cutaneous melanoma guidelines when counseling regarding prognosis and when considering a sentinel lymph node biopsy.

"The Benefit Of Positron Emission Tomography/Computed Tomography In Stage I And Stage II Melanomas With High-Risk Decisiondx-Melanoma Scores".

Early detection of melanoma is instrumental as the 5-year survival decreases from 93.3% to <50% when metastases are present.1-3 Distinguishing which patients require closer follow-up can be difficult for melanoma patients. Developments by Castle Biosciences' (Friendswood, TX) DecisionDx-Melanoma (DDx-M) use 31 melanoma associated genes to stratify melanomas into 4 classes with 1A having lowest risk of morbidity and mortality and 2B the highest.5 We assessed the benefit of providing additional 18FDG-PET-CT and brain MRI to genetically high-risk patients who may have otherwise been overlooked. 297 patients at our institution had biopsies sent for DDx-M between 2014 and 2021. Patients found to have Class 2 melanomas received additional screening with yearly 18FDG-PET-CT scans and brain MRIs. Patients with Class 2 DDx-M scores and negative SLNB were included in the study. 66 met inclusion criteria and received imaging. Within 3 years of follow-up, 8/66 (12.1%) patients had metastases detected by 18FDG-PET-CT scans. No patients with stage IA or IB went on to develop metastases. 18FDG-PET-CT scans detect metastases in < 3% of the time when all stage I and II patients are scanned; however, by using DDx-M in our screening protocols, we achieved a detection rate of 12.1%.6,7 These patients went on to receive treatment and would have otherwise progressed undetected, leading to higher morbidity and mortality. We suggest all patients with initial stage II or above melanomas receive a DDx-M score and those with class 2 receive yearly 18FDG-PET-CT/brain MRI imaging.

Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax Combined with Hypomethylating Agents

Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax Combined with Hypomethylating Agents

P191 Secukinumab demonstrates a consistent safety profile in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis over long term: updated pooled safety analyses

P191 Secukinumab demonstrates a consistent safety profile in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis over long term: updated pooled safety analyses

Abstract 5442: The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers

Abstract Introduction: Uveal melanoma (UM) is a highly aggressive eye cancer that leads to metastatic death in up to half of patients. UM has a propensity to undergo early micrometastasis prior to treatment of the primary tumor, with later emergence of overt metastatic disease. UM can be stratified into Class 1 (low metastatic risk) and Class 2 (high metastatic risk) using a prospectively validated 12-gene expression profile (GEP) molecular prognostication classifier. The Collaborative Ocular Oncology Group Study 2 (COOG2) is being conducted to prospectively evaluate new prognostic biomarkers in UM, including expression of PRAME, and prognostic driver mutations in BAP1, SF3B1, and EIF1AX. Methods: The COOG2 is a 24 center, prospective study of UM patients undergoing prognostic testing using the CLIA-certified DecisionDx-UM test (Castle Biosciences, Inc) between July 2017 and December 2019. Molecular analysis is performed on residual clinical samples. Data collected include clinical annotations, patient outcomes, GEP, PRAME status, and mutations in BAP1, SF3B1, and EIF1AX. Results: To date, there are 1300 participants enrolled. The baseline characteristics are as follows: 52% male, and 48% female; 87% non-Hispanic, 3% Hispanic, and 10% unknown. GEP classification is 66% class 1 and 34% class 2. PRAME status is 68% PRAME (-) and 32% PRAME (+). Targeted sequencing has been performed on 650 samples and is being analyzed. Conclusions: The COOG2 will establish a new standard of prognostic testing accuracy from a single fine needle biopsy in UM. The resulting integrated prognostic testing platform will be used as a stratification tool for entry into clinical trials of adjuvant therapy in high-risk patients. Citation Format: Christina L. Decatur, Michael A. Durante, Zelia M. Correa, Thomas M. Aaberg, Prithvi Mruthyunjaya, Amy C. Schefler, J. William Harbour. The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5442.

Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictor of Survival and Response to Therapy in Patients Treated with Immune Checkpoint Inhibitors

Background: Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients benefit, there is a strong need for predictive biomarkers. The aim of this study was to analyze the predictive capacity of neutrophil-to-lymphocyte ratio (NLR) in cancer patients treated with ICI, and to analyze the predictive value of combining NLR with tumor mutational burden (TMB). Methods: Retrospective cohort study of patients treated during 2015-2018. A total of 1714 patients with 16 different cancer types, who had complete blood count within 30 days prior to first ICI infusion, and whose tumors underwent next-generation sequencing were included. Overall survival, progression-free survival, response to ICI, and clinical benefit (response or stable disease ≥6 months) were the primary endpoints. Findings: Patients with NLR in the top 20th percentile within cancer type had significantly poorer overall survival (HR = 2·17; 95% CI, 1·89-2·50; P<0·001), progression-free survival (HR = 1·60; 95% CI, 1·41-1·81; P<0·001), response rate (18% vs 29%; P<0·001), and clinical benefit rate (21% vs 35%; P<0·001). Consistent results were obtained stratifying by cancer type. In multivariable analyses, NLR and TMB demonstrated independent association with clinical benefit. A combined variable of NLR and TMB was strongly associated with outcome. The probability of clinical benefit from ICI was 4 times higher in the NLR-low/TMB-high group compared to the NLR-high/TMB-low group (OR = 3·88; 95% CI, 2·72-5·54; P<0·001). Interpretation: In cancer patients, higher NLR was associated with poorer survival and lower likelihood of response to ICI. NLR is a suitable candidate for a cost-effective and widely accessible predictive biomarker, and can be combined with TMB for additional predictive capacity. Funding Statement: Fundacion Alfonso Martin Escudero (to CV), NIH K08 DE024774 and R01 DE027738 (to LGTM), and the NIH/NCI Cancer Center Support Grant P30 CA008748. Declaration of Interests:DH receives funding from AstraZeneca. MAP reports consulting fees from BMS, Merck, Array BioPharma, Novartis, Incyte, NewLink Genetics, and Aduro, honoraria from BMS and Merck, and research support from RGenix, Infinity, BMS, Merck, Array BioPharma, Novartis, and AstraZeneca. ANS reports advisory board position with BMS, Immunocore, and Castle Biosciences, and institutional research support from BMS, Immunocore, and Xcovery. VPB is a recipient of an immuno-oncology translational research grant from Bristol-Myers Squibb and is an inventor on a patent application related to work on neoantigen modelling. AMC reports advisory board position with Springworks Therapeutics. JJS has received travel support from Intuitive Surgical Inc. for fellow education and has served as a clinical advisor to Guardant Health, Inc. SGP has a patent PCT/US2016/026717 Methods of Cancer Detection Using PARPIFL pending, holds equity in Summit Biomedical Imaging, has a patent US 10,016,238B2 Apparatus, system and method for providing laser steering and focusing for incision, excision and ablation of tissue in minimally-invasive surgery, and holds equity in ColdSteel Laser Inc. NR reports research support from Pfizer and BMS, and consulting fees from REPARE Therapeutics, Mirati Therapeutics and Illumina. AZ reports honoraria from Illumina. TAC acknowledges grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H, and Eisai, has served as an advisor for Bristol-Myers Squibb, Illumina, Eisai, and An2H, holds equity in An2H, and is a co-founder of Gritstone Oncology and holds equity. LGTM reports laboratory research funding from Illumina, Inc. and AstraZeneca. Ethics Approval Statement: The study was approved by the Memorial Sloan Kettering Cancer Center institutional review board (IRB).