Citations

TPS2099 Background: Gliomas are the most common primary central nervous system (CNS) malignancy in adults, accounting for 26.3% of all brain tumors. Care at high volume centers is associated with an overall survival benefit, but access to in-person evaluations can be challenging due to disease-related neurological disability and loss of income. Telehealth represents a convenient and efficient alternative to in-person evaluations, but acceptability and comparative safety of this care delivery modality has not been prospectively evaluated among glioma patients undergoing chemotherapy. Methods: This single-arm non-randomized pragmatic clinical trial evaluates patient satisfaction with, and safety of video-enabled telehealth assessments compared to in-person evaluations for patients with glioma undergoing temozolomide chemotherapy. The study includes adult patients with a diagnosis of glioma requiring adjuvant temozolomide chemotherapy. Participants act as their own controls, alternating between in-person and telehealth assessments while undergoing chemotherapy dosed per standard of care. Monitoring labs are completed locally and transmitted electronically. For participants without access to Wi-Fi or a device (e.g. mobile phone or computer), cellular-enabled tablet devices are provided to facilitate appointments and completion of electronic study components. All participants who travel to in-person appointments are reimbursed for travel expenses. The primary outcome measure is patient satisfaction with care delivered, as measured by institutional Press-Ganey survey scores obtained following telehealth and in-person assessments. A key secondary outcome measure is completion rate of planned oral chemotherapy, tracked using a digital pill diary incorporated into our institutional electronic health record. The digital diary allows real-time tracking of chemotherapy adherence and adverse events experienced by participants. Other secondary outcomes include acute care utilization days following telehealth and in-person visits (defined as emergency department evaluations and days of inpatient stay), neurologic disability as measured by the Neurologic Assessment in Neuro-Oncology (NANO) scale, and disease related quality of life measured by the EORTC QLQ-C30. All participant surveys are self-reported and completed electronically. This decentralized pragmatic clinical trial provides unprecedented, prospective real-world data on utilization of telehealth services compared to in-person visits for patients undergoing chemotherapy for glioma. We expect the data generated to inform the design and conduct of future decentralized interventional neuro-oncology trials. NCT06625047 opened for enrollment in October 2024, 16 of 30 intended participants were accrued as of January 2025. Clinical trial information: NCT06625047 .

TPS2092 Background: Glioblastoma (GBM) is the most common primary brain malignancy in adults. GBM is universally recurrent and associated with dismal outcomes. Re-irradiation (reRT) is ideal for evaluating combination therapy for recurrent GBM (rGBM) due to its multifactorial mechanism of action, including downstream immunomodulatory activity. RT (especially multi-fraction) increases immunogenicity in preclinical models by promoting immune activation, immune migration, and antigen uptake. Additionally, a recent study demonstrated enhanced PD-L1 expression in the glioma tumor microenvironment (TME) following RT, and combining stereotactic RT with a PD-1 inhibitor improved survival in murine models. Retifanlimab is a humanized monoclonal anti-PD1 IgG4 antibody that received FDA approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma. Bevacizumab, an anti-VEGF antibody, is a treatment for radiation necrosis/cerebral edema with less immune suppression than corticosteroids. In a previous Phase 2 study, hypofractionated RT (HFRT), retifanlimab, and bevacizumab was associated with a 9-month overall survival (OS) rate of 71.4%. To demonstrate the efficacy of this regimen compared to HFRT and bevacizumab, we have designed a new randomized controlled Phase 2 trial. We hypothesize that combination reRT with retifanlimab will produce a more robust anti-tumor immune response and improve OS compared to reRT without retifanlimab. Methods: This is a multicenter, open-label, randomized, controlled Phase 2 study of retifanlimab, bevacizumab, and HFRT for adult patients with rGBM. Patients are randomized 1:1 to the experimental (bevacizumab + retifanlimab + HFRT) or control cohort (bevacizumab + HFRT). Key eligibility criteria include age ≥ 18 years, Karnofsky performance status ≥ 60, ≥ 4 months since administration of any prior bevacizumab, and dexamethasone dose ≤ 4 mg at the time of randomization. The primary endpoint is 9-month OS. Secondary endpoints include OS, progression-free survival, objective response rate, neurologic assessment by NANO criteria, and adverse events profile. Protocol treatment will continue up to two years, or until progression or intolerable toxicity. Survival follow up will continue every two months, up to four years. Seven of the planned 94 patients have been enrolled as of submission on 1/28/25. Clinical trial #: NCT06160206. Funding provided by Incyte. Clinical trial information: NCT06160206 .

ABSTRACT As the treatment paradigm for Waldenström macroglobulinemia (WM) continues to evolve, the debate surrounding the prioritization of depth of response versus disease control as therapeutic goals gains significant relevance. However, the impact of depth of response from fixed‐duration therapy on overall survival (OS) was unclear. This multicenter study evaluated the prognostic impact of depth of response using a landmark survival analysis. A total of 440 patients with WM treated with frontline fixed‐duration regimens were included. Attaining a major response (MaR) was associated with superior outcomes, including significantly longer OS. The estimated 5‐year PFS rates for patients with MaR at 6 months versus not were 50% versus 32%, respectively, p < 0.001, and the estimated 5‐year OS rates for patients with MaR at 6 months versus not were 89% versus 70%, respectively, p < 0.001. In a multivariable analysis, MaR at 6 months was independently associated with superior PFS (HR 0.66, p = 0.007) and OS (HR 0.28, p < 0.001). Similar results were seen when considering deeper responses (CR + VGPR vs. PR). Depth of response at 6 months is an important prognostic marker in WM and an independent predictor of PFS and OS. These results support its utilization as a suitable endpoint in clinical studies in WM.

Abstract Background: DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for hematological neoplasms. In this study, we make use of a natural inflammatory response occurring during COVID-19 to define the impact of these mutations on inflammation and outcomes. Methods: A cohort of 243 community-based patients (Olmsted County, MN) with COVID-19 were identified. CH status was determined on PBMC using error corrected sequencing (lower detection limit 0.5% VAF). In a subset of patients, we use multi-omics interrogation of the genome, transcriptome, and epigenome at single cell (sc) resolution along with DNA methylation, in PBMC, from patients with COVID-19 and CH. Results: We detected 97 CH mutations in 72 (29.6%) of 243 patients with COVID-19. The most frequent being DNMT3A (n=30, 30%) and TET2 (n=26, 28%). The presence of CH negatively impacted overall survival when restricted to TET2 and DNMT3A mutations. However, only DNMT3Amt CH retained age and comorbidity independent prognostication (HR 2.84, p = 0.022). We then assessed for changes in DNA methylation using Illumina MethylationEPIC array on patients with COVID-19 and DNMT3A (n=3) or TET2mt (n=4) CH. Site specific DNA methylation changes revealed significant loss of methylation in DNMT3Amt CH in comparison to TET2mt patients, with 10,944 hypomethylated and 1,160 hypermethylated sites. We found that actively transcribed states (Tx, TxWk) were more commonly hypomethylated in DNMT3Amt CH while enhancers (Enh) and promoters (TssA, TssAFlnk) were more commonly hypomethylated in TET2mt CH. We then conducted scDNA-seq in DNMT3Amt (n=3) and TET2mt (n=1) CH in COVID-19 and observed that while in TET2mt CH, mutations were largely restricted to classical and intermediate monocytes, in DNMT3Amt CH, mutations were seen in myeloid and lymphoid lineage cells. We performed scRNA-seq on patients with COVID-19 and DNMT3A (n=3) or TET2mt (n=6) CH. Differential gene expression analysis identified 1,569 upregulated genes in DNMT3Amt patients and 205 downregulated. Pathway analysis demonstrated an upregulation of genes involved in T cell survival, function, and inflammation in DNMT3Amt patients compared to TET2mt patients with a significant overexpression of GIMAP1, GIMAP4, IRF2, IL32 in multiple cell types. We correlated transcriptomic changes with chromatin accessibility using the 10X Genomics Multiome platform to profile both gene expression and open chromatin from the same samples. Analysis of global distribution of cut sites and differentially accessible peaks showed increased chromatin accessibility in DNMT3Amt CH, especially CD4+ T lymphocytes and NK cells. Conclusion: We demonstrate an age, sex, and comorbidity-independent adverse impact on mortality associated with DNMT3Amt CH in the context of COVID-19 and highlight transcriptomic and epigenetic differences between DNMT3A and TET2mt CH, with single cell resolution. Citation Format: Jenna A Fernandez, Wazim Mohammed Ismail, Moritz Binder, Terra Lasho, Susan M. Geyer, Amelia Mazzone, Christy M. Finke, Abhishek Mangaonkar, Jeong-Heon Lee, Liguo Wang, Vernadette A. Simon, Fariborz Rakhshan Rohakthar, Amik Munankarmy, Jonathan J. Harrington, Melissa R. Snyder, Keith D. Robertson, Alexandre Gaspar-Maia, Mrinal Patnaik. Divergent impacts of DNMT3A and TET2 mutant clonal hematopoiesis on COVID-19 related outcomes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr A012.

666 Background: In the phase 3 CABINET trial (NCT03375320), cabozantinib (CABO) significantly prolonged median progression-free survival (PFS) compared to placebo (PB) in patients with advanced, previously treated, progressive extrapancreatic NET (epNET) [HR 0.38 (95% CI, 0.25-0.59, P<0.0001)] and pancreatic NET (pNET) [HR 0.23 (95% CI, 0.12-0.42, P<0.0001)] (Chan et al., NEJM, 2024). In this analysis, we focus on outcomes of patients with epNET arising in the GI tract. Methods: Patients with locally advanced or metastatic epNET or pNET were randomized 2:1 in separate cohorts to receive CABO 60 mg daily vs PB. The epNET cohort included patients with tumors arising in the GI tract (not including pancreas), lung, unknown primary, and other rare primary sites. In this subgroup analysis of the epNET cohort, patients with GI NET were included. Eligibility included progression by RECIST within 12 months (mo) prior to registration, ≥ 1 prior systemic therapy. Primary endpoint: PFS by blinded independent central review (BICR). Secondary endpoints: objective response rate, overall survival, safety. Results: 116 of the 203 patients in the epNET cohort had GI NET (CABO, n=70; PB, n=46). Median age was 66 yrs; females: 46%; G1/G2/G3/unknown grade: 35%/57%/6%/2%. ECOG performance status: 0/1-2: 43%/57%. White race: 86%. The most common primary tumor locations were ileum/cecum (54%), small intestine with location not specified (20%); non-cecum colon or rectum (11%), stomach (4%); duodenum (3%); jejunum and nonspecified midgut site (3% each). Prior systemic therapies included somatostatin analogs (SSA) (100%), everolimus (59%); Lu-177 dotatate (77%); temozolomide +/- capecitabine (16%). In patients with GI NET, CABO was associated with improved PFS by BICR compared to PB (stratified HR, 0.50; 95% CI: 0.28-0.88, 1-sided stratified log-rank P=0.007). Median PFS with cabozantinib was 8.5 mo (95% CI, 6.0-16.7) compared to 5.6 mo (95% CI, 3.9-11.0) with PB. CABO demonstrated potential benefit in patients with midgut GI NET and across clinical factors including grade, functional status related to hormone secretion, concurrent SSA use, and prior therapy with Lu-177 dotatate or everolimus. The most frequent grade 3/4 adverse events attributed to therapy with CABO included hypertension (19%), diarrhea (13%), fatigue (10%). Conclusions: CABO is associated with improvement in PFS compared to PB in patients with advanced GI NET. Potential benefit was observed across clinical factors including grade, functional status, concurrent SSA, and prior treatment. The safety profile for CABO in patients with GI NET is consistent with that previously reported. Support: U10CA180821, U10CA180882; U10CA180820 (ECOG-ACRIN), U10CA180868 (NRG Oncology), U10CA180888 (SWOG); Exelixis; https://acknowledgments.alliancefound.org . Clinical trial information: NCT03375320 .

Background: Contemporary questions about treatment and outcomes of patients (pts) living with multiple myeloma (MM) demand efficient and timely evidence generation methods, where real-world/ everyday practice data can play an important role. Relevant potential applications include understanding and addressing disparities in treatment access, mitigating toxicities of novel therapies while maintaining quality of life, appropriately sequencing treatments within long-term management strategies, and disseminating and appropriately using surrogate endpoints in practice, such as minimal residual disease. However, existing real-world data (RWD) repositories are limited by an inability to implement interventions in response to issues identified through retrospective data analysis, which is pivotal for the use of newer therapies. The ASH Research Collaborative (ASH RC) MM Data Hub Program was developed to address these gaps. Methods: We developed a multicenter network of US-based tertiary academic medical centers, engaging site clinicians, patients, biostatisticians, informaticians, and data scientists. Initial activities included constructing a shared real-world MM data model comprised of consensus core data elements. Pt data from each site, dating back to at least 2019, is currently being entered through electronic case report forms, batch uploaded utilizing existing institutional data repositories, and soon direct electronic health record import in standard data acquisition formats. Data are aggregated in the Data Hub and shared in a confidential Site Portal with each site. The Portal allows sites to track their own pts, analyze outcomes, and identify ways to improve the quality of care provided to individuals living with MM. We also developed an innovative evidence generation learning community of site clinicians who meet monthly and collaborate on the “COVID-19 OutcomeS in Myeloma and the Impact of VaCcines (COSMIC)” study, a prospective, decentralized observational study that rapidly accrued pts and collects relevant practice information. The group also shares best practices in study conduct to accelerate study enrollment and execution. Results: The MM Data Hub Program now contains twelve centers: Memorial Sloan Kettering Cancer Center, Mayo Clinic, Icahn School of Medicine at Mount Sinai, University of California San Francisco, University of California Davis, Medical College of Wisconsin, Barbara Ann Karmanos Cancer Institute, University of North Carolina Medical Center at Chapel Hill, Emory University Hospital, Washington University School of Medicine in St. Louis, Dana-Farber Cancer Institute, and Atrium Health. From this Network, six centers have contributed data from 8,824 pts (2,825 with sufficiently complete data are included in this analysis). The median age at time of MM diagnosis is 63, and of the 627 deceased pts, the median age at death is 70.6 years, with median time to death from first MM diagnosis of 6 years. The proportions of pts by decade of diagnoses are 34.9% from 2020-2024; 57.6% from 2010-2019; 7.3% from 2000-2009; and 0.9% prior to 2000. 83.1% of pts had a diagnosis of plasma cell myeloma (non-light chain), and 14.4% of pts had a diagnosis of light chain myeloma. 42.3% of pts are female, and the self-reported patient races are: 85.0% white; 9.2% black or African; and 4.3% all other races (race was not documented in 1.5% of pts). 2.8% of pts are of Hispanic ethnicity. Participant data files are currently undergoing completion and cleaning procedures; the analysis will include updated results at the meeting, and a Network-wide analytic data set will be available for initial retrospective data analyses in early 2025. The COSMIC study opened for enrollment on January 22, 2024, and completed enrollment of 200 pts on May 17, 2024. Conclusions: The ASH RC Data Hub MM Program launched in 2023 and is comprised of 12 sites that collectively have contributed participant files for 8,824 pts thus far. Utilizing the structure of the Network, we successfully implemented and established the feasibility of collecting data directly from pts electronically to monitor SARS-CoV-2 vaccines and COVID-19 related outcomes. The Program serves as a successful proof-of-concept model, providing an enduring RWD resource and a prospective evidence generation platform for the myeloma community.

Background: The COVID-19 pandemic had an outsized impact on individuals with immune compromise, such as multiple myeloma, leading to increased rates of severe COVID, hospitalization, and death in these groups. The pandemic also demonstrated the need for rapid and efficient evidence generation to address rapidly changing medical needs and accelerated the use of innovative trial designs to accomplish this goal. Methods: We designed and established a prospective, decentralized study within a site-based provider network, COVID-19 OutcomeS in Myeloma and the Impact of VaCcines (COSMIC), for patients with multiple myeloma at ASH Research Collaborative sites to monitor outcomes related to COVID-19 infection and vaccination. The direct-to-patient approach was accomplished using a study application accessed with a QR code provided to patients during usual clinical care. All study activities occurred within the patient portal at Baseline, Day 30, and Day 180, minimizing burden on site personnel and staff. Study activities included eligibility confirmation, consenting, electronic health record (EHR) data permissions, and patient-reported outcome (PRO) surveys. PRO data (EORTC QLQ-C30, EORTC QLQ MY-20) were made available to clinicians through the portal to visualize results from their patients. Patients shared if they received a COVID-19 vaccination or booster and if they had a COVID-19 infection. Patients with a history of COVID-19 infection included method of confirmation and if hospitalization was required. Patients were provided compensation for participation. Automated text and email messages were sent at three separate intervals: 24 hours, Day 8, and Day 15 for participants who initiated but did not complete study activities. A personal email reminder per participant was sent for those whose second study visit window was approaching. ASH Research Collaborative clinicians met regularly to share best practices related to enrollment and study conduct, thereby creating an innovative evidence generation learning community. We studied the feasibility of data collection in a decentralized format by focusing on the number of participants who interacted with the system, those who consented, and those who completed baseline PRO assessments. Results: The COSMIC study rapidly accrued and consented 200 patients from eight participating ASH Research Collaborative sites over four months (1/22/2024 through 5/17/2024): 69% self-reported as non-Hispanic White (NHW). Of enrolled participants, 57.5% opted to permission sharing of their EHR data, which included disease and treatment-related clinical data, laboratory results, pathology reports, and imaging reports. A total of 196 patients (98%) provided demographic and COVID-related disease and vaccine data at baseline; nearly all of these patients (n=195) provided baseline PRO data, and 150 patients provided further information at Day 30 at the time of this analysis. Those who did not provide Day 30 data were not significantly different from those who did in terms of age (median: 68 [no Day 30 data] vs. 67 [Day 30 data] years; p=0.44), sex (41% [no Day 30 data] vs. 47% [Day 30 data] Female; p=0.47), or race (65% [no Day 30 data] vs. 71% [Day 30 data] NHW; p=0.60). A higher proportion of Hispanic patients were retained at Day 30 (13/15=87%) vs. 78% of non-Hispanic patients or those who declined reporting ethnicity (2/7=29%; p=0.007). COVID-19 vaccination data were submitted by 196 patients, 186 of whom had ever received a COVID-19 vaccination. Data on number, type, brand, and dates for these vaccinations were provided. Conclusions: The COSMIC study conducted by the ASH Research Collaborative was able to rapidly accrue a diverse cohort of patients using a decentralized workflow within a site-based provider network, with high consent and compliance rates. This platform, and the innovative evidence generation learning community of ASH Research Collaborative investigators and patients, sets a precedent to address a variety of real-world questions related to disease management, infections, vaccinations, and PROs in this population of patients with multiple myeloma.

Introduction The tumor ecosystem in multiple myeloma (MM) involves complex interactions among various cell types, including clonal plasma cells (PCs) and immune cells. Previous research has indicated that the bone marrow (BM) microenvironment's metabolite and lipid profiles differ between MM patients and those with precursor conditions. This study aims to explore if differences in cell composition, metabolic phenotype of clonal PCs, and the spatial organization of various cell types are linked to the early versus late progression of high-risk smoldering MM (SMM) to MM. Methods We identified high-risk SMM patients using the IMWG 20-2-20 criteria, focusing on early progressors (EP), who progressed to MM within one year, and later progressors (LP), who progressed after more than four years. Using a high-dimensional single-cell spatial imaging platform, CODEX (CO-Detection by indEXing), we identified clonal PCs and immune cell types as well as their metabolic phenotypes at the single-cell level, in paired FFPE BM samples at SMM diagnosis and at the time of progression to MM. Our validated panel included markers such as CD3e, CD4, CD8, CD14, CD20, CD31, CD38, CD45, CD66a, CD68, CD138, HLA-DR, ASCT2, pNRF2, GLUT1, LDHA, ATPA5, CPT1A, and Citrate synthase. We employed single-cell segmentation, artifact cleanup, signal thresholding, and spatial analysis. Repeated measure models accommodated multiple regions of interest (ROIs) per patient and accounted for potential intrapatient correlation, while Poisson models estimated incidence rate ratios (RR) of cell types. Spatial statistical models evaluated cell type segregation and integration at the time of SMM diagnosis. Results Single cell events were acquired from 6 unique SMM patients who had paired FFPE BM samples from the time of their SMM diagnosis and at the time of their progression to MM. There were 3 EP SMM patients (Time to Progression (TTP):8, 8, 10 mos) and 3 LP SMM patients (TTP: 51, 58, 117 mos). The median number of single cell events identified per patient slide sample was 104,390 (Range: 24,357 - 314,877). We identified 8 main cell types: PCs, CD4+ T-cells, CD8+ T-cells, B-cells, granulocytes, Monocyte/Macrophages and two groups of other immune cells. The PCs and the remainder of the non-PCs were further classified based on the expression of the following metabolic markers: ASCT2 (Glutamine importer), CPT1A (Fatty acid metabolism), GLUT1 (Glucose importer), LDHA (Glycolysis), Citrate synthase and ATPA5 (Oxidative Phosphorylation). There was a higher RR of granulocytes (RR 2.1, CI 1.6-2.8, p&lt;0.001) in EP compared to LP samples at the time of SMM diagnosis, but a lower RR of CD4 T cells (RR 0.40, CI 0.3-0.6, p&lt; 0.001). Focusing on metabolic phenotypes of the PCs, we observed higher incidence RR of most metabolic markers: ASCT2 (RR=1.77; p=0.032), ATPA5 (RR=1.25; p&lt;0.001), CPT1a (RR=2.42; p=0.015), and LDHA (RR 2.13; p&lt;0.001) in EP compared to LP samples at the time of SMM diagnosis. However, GLUT1 had a lower incidence RR in EP patients (RR=0.79; p&lt;0.001). The same modeling for non-PCs at the time of SMM diagnosis yielded higher expression of LDHA (RR=1.98; p&lt;0.001) and ASCT2 (RR=3.3; p=0.002). Using the x and y coordinates and the corresponding phenotype classifications, we performed spatial statistical modeling based on spatial point processes to generate aggregated measures of how different types of cells of interest interacted. CD4 T cells were more isolated in LPs compared to EPs (p =0.046). Segregation indices for PCs and CD4 T cells indicated that they were more integrated/collocated in EPs. Granulocytes were more isolated in EPs although the difference was not as pronounced (p= 0.07). PCs were more integrated with granulocytes (p=0.06) and B cells (p=0.07) in LP patients. Further analyses of paired samples at the time of progression to MM will be reported at the time of the presentation. Conclusion This study is the first to provide whole-slide, single-cell, spatial proteomic characterization of clonal PCs and immune cells in the FFPE BMs of high-risk SMM patients with varying progression times to MM. Distinct metabolic pathway markers in clonal PCs and their spatial relationships with immune cell subsets are closely associated with the risk of progression to MM. These findings illuminate the complex interactions between the metabolic states of clonal PCs and their spatial orientation relative to immune cells in the pathogenesis of MM.

Background: Data from the ASH Research Collaborative COVID-19 Registry for Hematology demonstrated that patients with multiple myeloma and other immune compromise had elevated risk for severe complications from COVID-19 infection. To address current evidence gaps and to demonstrate proof of concept for a pandemic preparedness and response network, the ASH Research Collaborative Multiple Myeloma Program developed a prospective, decentralized study within a site-based provider network to investigate COVID-19 infections, vaccinations, and quality of life in patients with multiple myeloma. Methods: We designed and established the COVID-19 OutcomeS in Myeloma and the Impact of VacCines (COSMIC) to study COVID-19 in patients with multiple myeloma at ASH Research Collaborative network sites. A study application was accessed with a QR code and shared with patients during usual clinical care. Patients provided consent, optionally gave permission for electronic health record data collection, and completed patient-reported outcomes (EORTC QLQ-C30 and MY20) at baseline, Day 30, and Day 180 through the study portal. Clinicians at participating sites facilitated study enrollment and shared best practices monthly to accelerate study execution. Study objectives related to feasibility of data collection in a decentralized format are reported in a separate abstract. Here, we report interim results related to SARS-CoV-2 vaccination history, COVID-19 infection, and how these relate to patient reported outcomes and clinical outcomes in enrolled participants. Results: The COSMIC study rapidly accrued and consented 200 patients from eight participating ASH Research Collaborative sites over four months (1/22/2024 through 5/17/2024). Consented participants' ages ranged from 29 to 93 years, with median of 67 years; 46% were female, 69% were non-Hispanic White (NHW), 17% were non-Hispanic Black (NHB), and 8% were Hispanic/Latino. Of the 196 patients who reported COVID-19 data, 111 (57%) reported at baseline that they had a history of COVID-19 infection, with 12 having required hospitalization for this (12/111=11%). Overall, 95% (186/196) reported a history of COVID-19 vaccination, where the median number of vaccinations was 4 (range: 1 to 6); 44 patients (23%) expressed willingness to discuss getting a yearly booster vaccine with their provider. At 1-month follow-up, there were 3 additional patients who reported a COVID-19 infection and 18 patients who received an additional COVID-19 vaccination. The baseline EORTC QLQ-C30 median Global Health Status/QOL score was 66.7 (mean=64.4, range: 8.3 - 100, n=196). This overall global QOL score was not significantly different between those who did vs. did not have a history of COVID-19 infection (mean [SD]: 63.7 [19.3] vs. 65.8 [17.6]; p=0.57). In analyses adjusted for age, biological sex, and race/ethnicity group, history of COVID-19 infection was not associated with HRQOL (odds ratio=0.93, 95% CI: 0.78 - 1.10; p=0.38). Data collection is ongoing and final study results will be reported at a later date. Conclusion: COSMIC is a prospective, decentralized study within a site-based provider network conducted by the ASH Research Collaborative Multiple Myeloma Program that demonstrates the feasibility of using an innovative evidence generation strategy to drive rapid accrual of patients to address a rapidly evolving area of need. The COSMIC study also provides proof of concept that a real-world evidence generation network can play an important role in national pandemic preparedness and response. The COSMIC experience reinforces the ability to accrue diverse patient populations representing the demographic of myeloma patients in the US.

Introduction: Health disparities negatively impact outcomes of patients (pts) with hematologic malignancies. Limited retrospective data correlating health disparities with lymphoma outcomes prohibit proper identification of reversible causes and elaboration of potential interventions. We present data from a coordinated effort between the National Clinical Trials Network (NCTN) cooperative groups (Alliance for Clinical Trials in Oncology [Alliance], Eastern Cooperative Oncology Group [ECOG], and the Southwest Oncology Group [SWOG]) to catalog the racial, ethnic, and socioeconomic characteristics of pts with lymphoma to better understand the quality of data collected, analyze selected health disparity indicators, and develop a prospective data collection tool. Methods: We conducted a retrospective analysis of demographic data from pts with lymphoma enrolled on 32 cooperative group therapeutic trials between 2005 and 2020. Special focus was placed on data regarding race, ethnicity, and proxies that help identify socioeconomic status (health insurance, residential zip code, Social Deprivation Index [SDI]). These were evaluated in relation to histology-based metrics from the Surveillance, Epidemiology, and End Results Program (SEER) Program with reported data through 2022. Here, our focus is to characterize baseline demographic and disparities data on the collection of these 32 NCTN lymphoma trials. Results: A total of 3,897 pts were included, with 3,406 non-Hodgkin lymphoma (87.4%) - 1,644 diffuse large B-cell (DLBCL, 48.3%), 905 follicular (26.6%), 669 mantle cell (19.6%), 113 primary central nervous system (3.3%), 75 T-cell (2.2%) - and 491 Hodgkin lymphoma (12.6%). Age at registration was available for 3,891 pts with median age 57.1 years (range: 18-92). The majority of patients were male (58.8%; one pt missing biological sex data). Race data were available for all but one patient, where most pts were white (W, 86.6%), followed by 246 African American (AA, 6.3%), 99 Asian (A, 2.5%), 13 American Indian or Alaska Native (AI, 0.3%), 8 Native Hawaiian or Pacific Islander (PI, 0.2%), 11 with more than 1 race reported (0.3%), and 145 with unknown/not reported race. Ethnicity data were unknown for 327 pts (8.4%) with 179 Hispanic or Latino (Hisp, 4.6%). Combined race/ethnicity data showed 3,010 non-Hisp white (NHW, 77.2%) and 219 non-Hisp black (NHB, 5.6%). For comparison, in the SEER database, 84.7% of all lymphoma cases were W, with 8.6% AA, 5.2% A/PI, 0.4% AI, and 1.1% unknown race, and with 13.9% of pts reported as Hisp. When focusing on the 804 pts enrolled on Alliance CALGB 50303 and ECOG-ACRIN 1412 studies, two randomized DLBCL studies, there was a more proportional representation of W and AA pts with DLBCL - 82.1% and 9.8% compared 84.6% and 7.7%, respectively, at SEER database, with 5.3% Hisp (with another 5.3% unknown) compared to 14.9% at SEER. Insurance information was missing in 113 pts. Of the remainder, 2,102 pts had private insurance only (55.6%), 549 with a mix of private and public (14.5%), 701 public only (18.5%, including 11.4% Medicare, 4.5% Medicaid, 0.8% both), and 166 self-pay (4.4%). Year-matched SDI score was available in 2,885 pts, where higher SDI scores = higher social deprivation. The total mean SDI score for the overall cohort was 42.5 with significant differences observed based on race/ethnicity and insurance type. Specifically, NHW were from less deprived areas (mean SDI=38.8) than NHB (66.4) or Hisp (65.5) (p&lt;0.0001). Those without insurance (mean SDI=52.6) or only public insurance (48.9) were located in areas associated with greater deprivation compared to pts with private (40.1) or public+private (38.8) insurance (p&lt;0.0001). Conclusion: To our knowledge, this is the largest retrospective catalog of racial, ethnic, and socioeconomic characteristics of pts with lymphoma enrolled on cooperative group therapeutic trials. The scope of NCTN cooperative group lymphoma studies provides a unique opportunity to assess novel therapeutic outcomes for patients representing racial, ethnic and socioeconomic subgroups with both common and rare lymphoma subtypes. From this resource, additional analyses on relationships between SDI, race/ethnicity, insurance coverage, disease subtype, and temporal trends will be presented. Support: U10CA180821, U10CA180882, UG1CA189823