MedStar Georgetown University Hospital Research Articles

Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy

SummaryIndolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the SSU72 gene. In addition, numerous genetic alterations that may have contributed to malignant transformation were identified in the tumor sample. (Funded by MedStar Georgetown University Hospital.)

Patients with hepatocellular carcinoma (HCC) who require multiple transarterial chemoembolization (TACE) treatments in quick succession and prediction of outcome.

e16208 Background: TACE has been one of the standard treatments for intermediate-stage HCC patients for over 20 years. The outcome of patients from TACE treatment is variable as the result of the differences in tumor burden, liver function, and comorbidities. Given the advancement made in systemic therapies for advanced-stage HCC, and emerging data on the combination of TACE and immunotherapy, there is an unmet need to identify patients with intermediate-stage HCC who may benefit from early introduction of systemic therapy. The purpose of the study is to identify clinical factors that predict poorer outcomes in patients who receive TACE treatment. Methods: This retrospective analysis is a single-institutional study involving patients from MedStar Georgetown University Hospital. The investigation includes 167 individuals diagnosed with HCC who underwent TACE from 2007 to 2021. The data compiled for analysis encompassed patient demographics, clinical features, risk factors, and treatment outcomes. The log-rank test is used to test whether there is a difference between the survival times of different groups. Results: 167 HCC patients, with 105 in intermediate/advanced BCLC stages B and C were included. The cohort, with a median age of 62, comprised 128 males and 43 females. Cirrhosis was seen in 83% of patients mostly due to viral etiology. Hepatitis C (58%) and hepatitis B (13%) were common, with 4% having both. The remaining 24% had cirrhosis from metabolic-associated fatty liver disease (MAFLD). The median overall survival (OS) durations for patients in BCLC-A (n = 62), BCLC-B (n = 64), and BCLC-C (n = 41) stages who underwent TACE as a component of their comprehensive treatment strategy were 67.9, 29.7, and 30.6 months, respectively (P = 0.035). In 64 subjects with BCLC stage B disease, patients who received 3 or more TACE treatments had higher OS (43.6 months) than those with two or fewer treatments (25.4 months, P = 0.042). Among the patients who had 2 or fewer TACE treatments, 6 patients had liver decompensation and discontinued treatment and 21 patients developed cancer progression and went on to receive systemic therapy. The median time to progression from the last TACE treatment was 5 months. Interestingly, among the patients who received 3 or more TACE treatments, 10 patients who had 3 or more TACE treatments within 6 months from the 1st TACE treatment had an mOS of 25.8 months while 25 patients who had 3 or more TACE treatments over a time span more than 6 months had a mOS of 49.4 months (P = 0.0186). Conclusions: Rapid disease progression in 6 months from the start of TACE treatment was predictive of aggressive tumor biology, and these patients may benefit from the early introduction to systemic therapy. Molecular biomarkers used to predict aggressive tumor biology are an unmet need for selecting patients to receive the combination of TACE and systemic therapy.

Patients with hepatocellular carcinoma (HCC) who require multiple transarterial chemoembolization (TACE) treatments in quick succession and prediction of outcome.

e16208 Background: TACE has been one of the standard treatments for intermediate-stage HCC patients for over 20 years. The outcome of patients from TACE treatment is variable as the result of the differences in tumor burden, liver function, and comorbidities. Given the advancement made in systemic therapies for advanced-stage HCC, and emerging data on the combination of TACE and immunotherapy, there is an unmet need to identify patients with intermediate-stage HCC who may benefit from early introduction of systemic therapy. The purpose of the study is to identify clinical factors that predict poorer outcomes in patients who receive TACE treatment. Methods: This retrospective analysis is a single-institutional study involving patients from MedStar Georgetown University Hospital. The investigation includes 167 individuals diagnosed with HCC who underwent TACE from 2007 to 2021. The data compiled for analysis encompassed patient demographics, clinical features, risk factors, and treatment outcomes. The log-rank test is used to test whether there is a difference between the survival times of different groups. Results: 167 HCC patients, with 105 in intermediate/advanced BCLC stages B and C were included. The cohort, with a median age of 62, comprised 128 males and 43 females. Cirrhosis was seen in 83% of patients mostly due to viral etiology. Hepatitis C (58%) and hepatitis B (13%) were common, with 4% having both. The remaining 24% had cirrhosis from metabolic-associated fatty liver disease (MAFLD). The median overall survival (OS) durations for patients in BCLC-A (n = 62), BCLC-B (n = 64), and BCLC-C (n = 41) stages who underwent TACE as a component of their comprehensive treatment strategy were 67.9, 29.7, and 30.6 months, respectively (P = 0.035). In 64 subjects with BCLC stage B disease, patients who received 3 or more TACE treatments had higher OS (43.6 months) than those with two or fewer treatments (25.4 months, P = 0.042). Among the patients who had 2 or fewer TACE treatments, 6 patients had liver decompensation and discontinued treatment and 21 patients developed cancer progression and went on to receive systemic therapy. The median time to progression from the last TACE treatment was 5 months. Interestingly, among the patients who received 3 or more TACE treatments, 10 patients who had 3 or more TACE treatments within 6 months from the 1st TACE treatment had an mOS of 25.8 months while 25 patients who had 3 or more TACE treatments over a time span more than 6 months had a mOS of 49.4 months (P = 0.0186). Conclusions: Rapid disease progression in 6 months from the start of TACE treatment was predictive of aggressive tumor biology, and these patients may benefit from the early introduction to systemic therapy. Molecular biomarkers used to predict aggressive tumor biology are an unmet need for selecting patients to receive the combination of TACE and systemic therapy.

Cross-cultural differences in diet and quality of life between Taiwanese and American women during breast cancer treatment.

e23187 Background: Limited research has examined the role of different food types (vegetables, fruits, meat, fat, and whole grains) on quality of life (QoL) among cancer patients undergoing active treatment. This study aimed to examine what different food intakes are associated with QoL among American and Taiwanese women who are newly diagnosed with breast cancer (BC). Methods: This ongoing observational study enrolled 77 American (Black, Latina, and non-Hispanic White) adult women from MedStar Georgetown University Hospital and 79 Taiwanese women from National Taiwan University Hospital. They were diagnosed with stage 0-III primary BC within six months prior to enrollment, were undergoing surgery, chemotherapy, and radiation, with no other cancers. Patient-reported overall health and QoL were assessed using the two global health items from the EORTC-QLQ30. Three random 24-hour diet recalls (two weekdays and one weekend) were administered using the NIH-developed ASA24 program. Linear regression was conducted to examine the associations between food categories and QoL outcome, adjusting for nationality, age, cancer stage, treatment type, body mass index, physical activities, financial problems, and appetite loss. Results: American and Taiwanese patients displayed differing food intake during BC treatment. Taiwanese patients consumed less starchy vegetables and total fat (both p < .01) than American patients, on average. Multivariate results indicated that QoL was positively associated with higher total vegetable intake (excluding starchy vegetables and legumes; β = 5.38, 95% CI: 0.22, 1.20), controlling for other food types and covariates. Starchy vegetables and legumes showed non-significant negative effects on QoL. QoL was positively associated with total fat intake (β = 0.11, 95% CI: 0.02, 0.21). Total meat, fruit, and whole grain intakes were not significantly associated with QoL. Conclusions: The associations between food intakes and QoL were not affected by nationality, regardless of food type. Non-starchy vegetables and adequate total fat intakes may support BC patients undergoing treatments. More research is needed to verify the identified associations and explore how cancer treatment affects the digestion of certain food types and their potential impact on QoL. This study provides cross-cultural insights into potential nutritional influence on QoL among patients undergoing cancer treatment.

Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Supportive Care of Hematopoietic Stem Cell Donors.

Supportive care needs for hematopoietic stem cell recipients have been studied. Less is known about the care needs of stem cell donors. Care challenges arise at donor selection, preparation for the donation, the donation procedure and the immediate and long-term after-care. Care needs were analyzed for 1,831 consecutive bone marrow and peripheral stem cell donors at MedStar Georgetown University Hospital between January 2018 and August 2023 in support of a review of the current literature. During the selection, related donors may experience psychological pressures affecting their motivation, while donation centers may be willing to accept co-morbidities in these donors which might preclude donation in unrelated peers. For bone marrow donations, it is important to select donors not only according to optimal genetic matching criteria but also according to suitable donor/recipient weight ratios, to facilitate sufficient stem cell yields. During the donation preparation phase, side effects and complications related to stem cell stimulation must be anticipated and managed for peripheral cell donors, while the pros and cons of autologous blood donation should be evaluated carefully for bone marrow donors. The stem cell donation procedure itself carries potential side effects and complications as well. Peripheral cell donors may require a central line and may encounter hypocalcemia, thrombocytopenia, and anemia. Bone marrow donors face risks associated with anesthesia, blood loss and pain. Post-procedure care focusses on pain management, blood cell recovery and the psychological support necessary to regain a high quality-of-life existence. Hematopoietic stem donors are giving part of themselves to save another's life. They deserve comprehensive supportive care to accompany them throughout the donation process.

Investigating Metabolic and Immunologic Consequences of Nucleotide Substitutions in Acute Myeloid Leukemia

Background Stressors, conventionally defined as cell extrinsic factors with the ability to promote clonal evolution, have been implicated as modulators of cancer development and progression. Smoking has previously been linked to unique single-base substitutions (SBSs), which may facilitate the development and progression of acute myeloid leukemia (AML). Similar to smoking in lung cancer, we previously reported unique C&amp;gt;A single-base substitutions (SBSs) in AML. SBS4 mutational signature (COSMIC database) is characterized by C&amp;gt;A transversions and may induce “immunogenicity”. Interestingly, C&amp;gt;A associates with G&amp;gt;A in elderly AML with previous smoking history (Patel, ASH, 2022). In recent years, high body mass index (BMI) has been associated with risk for clonal hematopoiesis (CH). However, a SBS correlation with metabolic parameters (i.e. lipid studies and BMI) remains uncharacterized. In this study, we aimed to: (1) confirm the association of smoking with C&amp;gt;A and G&amp;gt;A SBSs in an expanded cohort of leukemia patients and (2) to investigate metabolic and immunologic factors associated with these SBSs among patients with leukemia. Methods After IRB approval, we conducted a retrospective analysis of AML patients (pt) from Baylor and MedStar Georgetown University Hospital (MGUH). Genetic data using next generation sequencing (NGS), as well as demographic and clinical information was obtained. For patients from MGUH, FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the NCBI gene database. MHC I binding neopeptides were identified by mapping FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. SBSs with neopeptides that exhibited binding were grouped for further analysis of associations. Descriptive statistics were obtained using SAS software. Results Our expanded database included 85 pt with AML that had NGS performed at diagnosis. This increased the number of SBSs in our database from 148 to 213. Median age was 64.8 years (y) (range, 22-89). 42/85 patients (49.4%) had a positive smoking exposure. 41/213 (19.2%) of SBSs were C&amp;gt;T, 14/213 (6.6%) were C&amp;gt;A, 12/213 (5.6%) were G&amp;gt;C, 68/213 (31.9%) were G&amp;gt;A, 12/213 (5.6%) were A&amp;gt;C, 8/213 (3.8%) were A&amp;gt;T, 25/213 (11.7%) were G&amp;gt;T, 13/213 (6.1%) were A&amp;gt;G, 4/213 (1.9%) were T&amp;gt;A, 6/213 (2.8%) were T&amp;gt;C, 8/213 (3.8%) were C&amp;gt;G, and 2/213 (0.9%). 4/80 (5%) of G&amp;gt;A transitions were in pts age &amp;lt;40y, 18/80 (22%) age 40-59 y, and 58/80 (73%) &amp;gt;60y ( Fig 1A). Smoking significantly increased association with C&amp;gt;A transversion rate from 2.44% to 12.94% ( p=0.003). C&amp;gt;A combined with G&amp;gt;A showed an increased smoking rate of 50.59% vs 29.27%( p=0.002). When compared with patients without a smoking exposure, patients with C&amp;gt;A or G&amp;gt;A mutations and a smoking exposure had significantly higher total cholesterol of 165.2mg/dL compared to 125.8mg/dL ( p=0.02) and LDL of 101.8mg/dL compared to 74.5mg/dL ( p=0.04). Interestingly, higher frequency of G&amp;gt;T, (previously recognized to be associated with oxidative damage) was observed among AML patients aged 40-59 exhibiting higher body mass index (BMI) ( Fig 1B). Given dominance of G&amp;gt;A expression in older AML pt, we investigated MHC class I neopeptide immunogenicity initiated by G&amp;gt;A mutations as a suggestion of functional interference. Among pathogenic G&amp;gt;A variants demonstrating TCR-reactivity, 1/18 (5.6%) vs 7/21 (33.3%) neopeptides were observed in AML pt less than 60 y vs older than 60 y ( p = 0.03). Discussion Our data confirm the association of smoking exposure with C&amp;gt;A and G&amp;gt;A mutagenicity. Subsequent analysis demonstrated a significant association with increased TC and LDL levels, indicating an altered lipidome may affect the acquisition of these mutations in AML patients with smoking exposure. We have also seen that G&amp;gt;A is enriched in older AML patients. In this pt subgroup, our data suggests that neopeptides derived from G&amp;gt;A SBS retain immunogenic potential. While this has been previously associated with aging, other etiologic associations have yet to be established. Additionally, younger obese AML pt exhibit increased susceptibility for G&amp;gt;T mutagenesis possibly as result of oxidative stress. Continued work is needed to elucidate the spectrum of stressors associated with mutational signatures in AML and their underlying mechanisms, as this will have important biologic implications for preventative and therapeutic interventions.

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (&amp;gt;38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

Timing of Thrombosis with Myeloproliferative Neoplasm Diagnosis Among Veterans and Civilians

Rates of Arterial (AT) and Venous Thrombosis (VT) are increased in Veterans with Myeloproliferative Neoplasms (Vet-MPN), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), compared to matched controls (J Clin Oncology 2023 41:16_suppl, 7011). The timing of first AT or VT episode in Vet-MPNs remains undefined when compared to Civilians with MPN (Civ-MPN). These findings could elucidate optimal timing for risk mitigation strategies to prevent thrombotic complications and should help to determine duration of thrombotic risk and need for systemic anticoagulation prophylaxis. The Veterans Affairs Informatics and Computing Infrastructure (VINCI) database was queried from January 1, 2006 to January 26, 2023 to identify Vet-MPNs, AT, and VT through ICD-9 and -10 codes. This process yielded 2,752 Vet-MPN and 583,803 Veterans without MPN from Illinois, the state most representative of the US population. These cohorts were compared to data derived from a retrospective chart review of Civ-MPN cared for between January 1, 2019 to December 31, 2022, at MedStar Georgetown University Hospital and MedStar Washington Hospital Center. Service-Connected Exposures (SCE) to potential carcinogens among Veterans were verified through their duration and location of service. We subdivided time to first AT and VT from MPN diagnosis as follows: more than 3 months prior to MPN diagnosis, within 3 months of diagnosis, 3 months to 1 year post diagnosis, 1 to 5 years, and more than 5 years after MPN diagnosis. Mean data from various cohorts were analyzed utilizing Fisher's exact test. Vet-MPN experienced a statistically higher incidence of AT compared to Civ-MPN (p=.0019) and Civ-MPN experienced a statistically higher incidence of AT compared to Veterans without MPN (p=0.02) which served as a control. In contrast, there was a higher incidence of VT among both Vet- and Civ-MPN cohorts compared to Veterans without MPN (p&amp;lt;.0001) (Table 1). The mean ages at MPN diagnosis and onset of first AT were similar (≥63 years) in both Civ- and Vet-MPN. In contrast, the mean age of MPN diagnosis and age of first VT were considerably earlier for Civ-MPN (51 years) versus both Vet-MPN with VT and Veterans without MPN with VT (≥67 years). There was a higher prevalence of hypertension, hyperlipidemia, diabetes, heart failure, and smoking among Veterans with or without MPN compared to Civ-MPN with either AT or VT (Table 1). A trend toward statistical significance was observed for the presence of hypertension and hyperlipidemia (p=0.049 and p=0.02, respectively) in Vet-MPN compared to Civ-MPN, while Veterans without MPN had a statistically higher prevalence of hyperlipidemia (p=0.02) and heart failure (p=0.001) in AT. Notably, a trend toward statistical significance in VT was observed for the presence of diabetes among all Veterans with or without MPN compared to Civ-MPN (p=0.01 and p=0.007, respectively). There was a biphasic distribution in time to onset of first AT and VT in all Vet- and Civ-MPN cohorts (Figure 1). There was a higher cumulative incidence of first AT and VT in Vet-MPN at more than 3 months prior to MPN diagnosis compared to Civ-MPN with AT and VT (Figure 1). On the other hand, the Civ-MPN cohort had a late surge of first VT more than 5 years after MPN diagnosis compared to the other MPN cohorts. A biphasic distribution in time to onset of first AT and VT was also observed among the Vet-MPN cohort when stratified by SCEs from World War II, the Korean War, the Vietnam War, and the Gulf War. The vast majority of both AT and VT in Vet-MPN from all SCE examined experienced onset of thrombotic events more than 3 months prior to MPN diagnosis. Most VT in Gulf War Vet-MPN occurred within 3 months of MPN diagnosis. In conclusion, the predominant risk for developing thrombotic complications in MPN, particularly in Vet-MPN, occurs in a biphasic pattern, beginning more than 3 months prior to MPN diagnosis and becoming apparent again at more than 5 years after MPN diagnosis. These findings suggest that the MPNs convey an enduring hypercoagulability potential throughout the natural history of the disease. There appears to be an accelerated onset of thrombotic complications earlier in the course of disease in Vet-MPN, perhaps reflecting their SCE with toxic carcinogens. More work is necessary to determine epigenetic influences on MPN natural history.

The Human Leukemia Immunopeptidome Is Driven By Pathogenic Molecular Variant Biotypes

Background Historically, acute myelogenous leukemia (AML) has been characterized as having a low somatic mutational burden and is predicted to have low neoantigen levels compared to solid tumors. However, recent data has shown that AML is an immunogenic malignancy and oncogenic driver mutations promote immune escape through immunoediting. Downregulation of human leukocyte antigen (HLA) class II HLA-DRB1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 gene expression on leukemia cells has previously been associated with immune escape in AML following allogeneic hematopoietic stem cell transplantation (allo-HCT). While allo-HCT and cellular therapies are well-known potentially curative treatment options in AML, the human leukemia immunopeptidome has still not been well characterized. Here, we sought to uncover the human leukemia immunopeptidome by detecting differential major histocompatibility complex (MHC) class I neopeptide expression using molecular biotype subgroups. Methods We conducted retrospective analysis on 31 patients with hematopoietic malignancies including AML, chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), MDS, chronic myelogenous leukemia (CML) and other hematopoietic malignancies (i.e. NK cell leukemia) at MedStar Georgetown University Hospital. Mutations were identified using next generation sequencing and separated into the following annotated molecular biotypes based on the mechanism of pathogenesis: Group 0 (G0) DNA repair, G1 splicing, G2 transcription factor, G3 kinase activation, G4 epigenetic modification, G5 chromatin remodeling, G6 cohesin, G7 tumor suppressor (i.e. p53), G8 telomere maintenance, G9 histone modification, G10 nucleotransport (i.e. NPM1) and G11 cell cycle regulation. FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the National Center for Biotechnology Information (NCBI) gene database. MHC class I binding neopeptides were identified by mapping patient FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. Neopeptides were grouped by % Rank and categorized as weak binding (WB) if &amp;gt; 0.5 and strong binding (SB) if ≤0.5. Descriptive and inferential statistics were performed using SAS. Results Thirty-one patients were evaluated including 17 AML (54.8%), 5 MDS (16.1%), 3 CMML (9.7%), 2 MDS/MPN (6.5%), 1 CML (3.2%) and 3 hematopoietic malignancies (9.7%). The median age was 65 years (range 28 -89); 43.8% were female and 43.3% were African American (AA). 144mutations were identified; thus far, 82 mutations have been subjected to FASTA NP_ protein extraction. The G3 biotype had the highest frequency of neopeptide bindings (n=59) followed by G2 (n=50) and G4 biotypes (n=42) ( Fig.1). Among patients with MDS, smokers were more likely to exhibit neopeptide binding compared to non-smokers (p=0.032). Patients with neopeptide binding had a longer median overall survival (mOS) compared to patients without neopeptide binding (mOS = 566 vs 114 days, p=0.0174) (Fig 2). Data exploration allowed isolation of a 54-year-old Asian male with Li-Fraumeni syndrome and p53 mutated AML who demonstrated high affinity neopeptide binding to HLA-B*39:01 with %Rank 0.08. Additionally, a 34 -year-old AA female with FLT3 mutated AML showed very high affinity neopeptide binding to HLA-A*29:02 with %Rank 0.007 as well as evidence of somatic HLA-A*03:01 deletion. Conclusions Pathogenic molecular variant biotypes constitute a novel immune signature, the human leukemia immunopeptidome. Smoking increased the likelihood of MHC class I neopeptide binding among patients with MDS. The presence of neopeptide binding predicted improved mOS in patients with myeloid malignancies. Further investigation of the human leukemia immunopeptidome may provide additional prognostic significance above that of standard molecular and cytogenetic risk stratification.

The predictive value of liver tests for the presence of liver metastases.

To analyze the predictive value of biochemical liver tests in patients with malignant melanoma, breast, colorectal or lung cancers at the time of diagnosis of liver metastases. A retrospective review of patients with the above-mentioned solid tumors at MedStar Georgetown University Hospital from 2016-2020. The highest optimal cutoff according to sensitivity and specificity for the presence of liver metastases was for AST ≥1.5×ULN for melanoma, lung, and breast cancers and ≥2×ULN for colorectal cancer, ALT ≥1.25×ULN for melanoma, breast and colorectal cancers and ≥1.5×ULN for lung cancer, and ALP ≥1.5×ULN for melanoma, breast and colorectal cancers. Using thresholds of liver enzymes above the ULN may improve the diagnostic accuracy for the presence of liver metastases.

High levels of expression of Trop-2 in thymic epithelial tumors

BackgroundTrophoblastic antigen 2 (Trop2) is a cell surface glycoprotein expressed in multiple types of cancers, including breast cancer, non-small cell lung cancer, and gastrointestinal cancers. Trop2 expression and the use of Trop2-directed therapy such as antibody-drug conjugate (ADC) have not yet been investigated in thymic epithelial tumors (TETs). MethodsPatients with TETs treated at MedStar Georgetown University Hospital were retrospectively identified. Of the patients for whom tumor samples and normal thymus tissue were available, immunohistochemistry (IHC) membranous staining for Trop2 and PD-L1 were performed. Positivity for Trop2 required at least 10% of the tumor cells to be stained, with an intensity scored of 1+ (weak), 2+ (moderate), and 3+ (strong). Cases with CPS ≥ 5% were considered positive for PD-L1. Results30 TET samples from 29 patients (17 patients with thymoma and 12 patients with thymic carcinoma) were identified. One patient with thymic carcinoma had two samples from different time points. From the same set of patients, 13 samples of normal thymus tissue were available. In normal thymus tissue, eight samples (62%) showed no positivity of Trop2, while five samples (38%) showed 1 + IHC staining. In the thymoma samples, four (24%) showed 0 or 1 + IHC staining, while 13 (76%) showed 2 + or 3 + staining. Of the 13 thymic carcinoma samples, three samples (23%) showed 1 + IHC staining while seven (54%) showed 2 + staining and three (23%) showed 3 + staining. There was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in thymoma or thymic carcinoma. ConclusionsTrop2 is readily expressed in TETS with a higher degree of expression in thymic carcinoma. The expression of Trop-2 was lower in normal thymic tissue compared with TETs. The increased expression of Trop-2 in TETs suggests that Trop2 is an attractive therapeutic target for Trop-2 directed therapy.

Discordant Race and Ethnicity Documentation in the Georgetown Multiple Sclerosis and Neuroimmunology Center (P4-9.005)

<h3>Objective:</h3> We aimed to evaluate the reliability of R/E documentation in the EHR of MedStar Georgetown University Hospital. <h3>Background:</h3> The incidence and prevalence of multiple sclerosis (MS) appears to vary by race and ethnicity (R/E), and prognosis has been reported to be worse in Black and Hispanic/Latinx MS patients compared to White MS patients. Frequently, studies rely on electronic health records (EHR), but discrepancies in R/E documentation may be a potential source of errors in health disparities assessment. <h3>Design/Methods:</h3> Self-reported data from the MS-ADVANCE study at Georgetown University was compared to demographics extracted from the MedStar Georgetown University Hospital EHR. Concordance was defined as the percent agreement between self-reported R/E and R/E demographic information found in the EHR. <h3>Results:</h3> R/E data from 197 participants in the MS-ADVANCE study were analyzed. Most participants self-reported as Non-Hispanic White (n=142), which generally matched EHR documentation (concordance 92.6%). Similarly, 86% of Non-Hispanic Black (n=43) and 100% of Asian individuals (n=2) were accurately identified in the EHR. However, only 2 of 8 self-identified Hispanic/Latinx patients were identified as such in the EHR (concordance 25%). <h3>Conclusions:</h3> This is the first study evaluating concordance of self-reported R/E information compared to EHR documentation in patients with MS. While concordance was generally good in most groups, R/E information in the EHR was often incorrect for Hispanic/Latinx patients. Because most epidemiological analyses extract data from electronic records, this considerable observed discrepancy in R/E documentation may impact our understanding of prevalence, incidence, and prognosis in Hispanic/Latinx individuals with MS. Since obtaining reliable demographic information is crucial to determine quality of care and health outcomes, improvement in data collection is necessary when exploring healthcare disparities in Hispanic/Latinx individuals living with MS. <b>Disclosure:</b> Dr. Manrique has nothing to disclose. Miss Peres Da Silva has nothing to disclose. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myer Squibb. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Peter Angelos Law Firm. Dr. Osborne has received publishing royalties from a publication relating to health care. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biogen. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mallinckrodt.

Differences in Stroke Outcomes and Experiences between White and Minority Patients and Providers (P7-5.029)

<h3>Objective:</h3> Our primary aim was comparing provider and patient surveys regarding stroke care. Our secondary aim was comparing patient responses by race/ethnicity. <h3>Background:</h3> Race disparities exist in treatment, lived experiences, and outcomes of stroke survivors. Stroke providers and patients differ in values and concerns during recovery. Aligning patient and provider concerns may foster better therapeutic relationships. <h3>Design/Methods:</h3> A 28-question patient survey and 25-question provider survey were created to gain insight into experiences with stroke care at MedStar Georgetown University Hospital (MGUH). Of 200 patients admitted to MGUH stroke service from September 2021 to March 2021, 39 completed the patient survey. All 40 providers (physicians and nurses from emergency medicine, neurology and critical care) completed their provider surveys. Statistical analyses included Fisher’s exact test. <h3>Results:</h3> White patients were older and had higher education than racial/ethnic minority patients but similar health-insurance status. Providers were mostly white and female. White patients agreed their health care team effectively communicated to understand their condition significantly more than minority patients (p=0.033). White patients perceived significantly more support from their health care team than minority patients (p=0.05). Providers viewed managing chronic stroke effects (77%) and difficulty following lifestyle changes (46%) as the biggest challenges in patients’ long-term care. Racial/ethnic minority patients expressed concern with understanding stroke risk factors (35%) and responsibilities at work and home (35%). White patients reported concerns managing effects of their strokes (33%), risks of recurrence (25%), and worries about home responsibilities (25%). <h3>Conclusions:</h3> This pilot survey-based study demonstrated differences in care experiences and post-stroke concerns between white and racial/ethnic minority patients. Most providers viewed managing chronic effects as the biggest challenge for patients, which was more consistent with white patients. Racial differences between providers and minority patients may contribute to differences in long-term stroke concerns. Limited by sample size, a larger multi-center study is planned to increase generalizability. <b>Disclosure:</b> Mr. Shankar has received personal compensation for serving as an employee of Medstar Georgetown. Ms. Sumling has received personal compensation for serving as an employee of Georgetown Medstar. Dr. Denny has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbott Laboratory. The institution of Dr. Denny has received research support from NIDDILIR. Dr. Denny has received publishing royalties from a publication relating to health care.

Abstract P4-03-42: Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer

Abstract Background: Early-onset breast cancer is typically defined as a diagnosis of disease before age 40-45. Prior studies have shown interesting associations between race and obesity on the incidence and prognosis of breast cancer. Data from the SEER program at the National Cancer Institute has shown increased mortality amongst African American women (0.2%) compared to Non-Hispanic White (NHW) women (0.1%) who were diagnosed with breast cancer at age 45 years or younger. This is despite a similar risk of diagnosis between racial groups of this age range (1.27%, 1.27%). Other large studies have shown that African American patients tended to present with more advanced disease had worse clinical outcomes. Our study sought to determine the impact of race and obesity on the diagnosis and prognosis of early onset breast cancer amongst the patient population at Georgetown University Hospital (GUH). Methods: We compiled a database of all new patients, 652 in total, seen at Lombardi Cancer Center at Medstar GUH from 10/2020- 6/2022. We reviewed patient charts in the EMR and documented age at diagnosis, race, ethnicity, stage at diagnosis, and BMI. The BMI was categorized by underweight (BMI &amp;lt; 18.5), healthy weight (BMI 18.5-24.9), overweight (BMI 25-25.9), obese (BMI 30-34.9), and morbidly obese (BMI ≥ 35). Stage at diagnosis was determined by comparing the pathology report with the NCCN guidelines version 4.2022. We identified 136 patients who were diagnosed at GUH at age 45 years old or younger and compared our findings to SEER data from 2017-2019. Results: Out of 136 patients who met our age criteria, 131 had racial data available: 29 AA (0.22), 68 NHW (0.52), 4 Hispanic (0.03), 30 Other (0.23). Out of the 34 patients with advanced disease (stage 3 and 4) 16 were NHW (0.47), 4 were AA (0.12), 2 were Hispanic (0.06) and 12 were Other (0.35). 131 patients had BMI data available: 5 underweight (0.04), 56 healthy weight (0.43), 41 overweight (0.31), 21 obese (0.16), and 8 morbidly obese (0.06). 18 patients with advanced disease were overweight or obese, out of which 11 were NHW (0.61), 3 were AA (0.16), 3 were Other (0.16), and 1 was Hispanic (0.06). Conclusion: In contrast with the SEER data, our study found that the patient population at GUH had a much higher proportion of Non-Hispanic White (NHW) patients who were diagnosed with advanced disease compared to African American (AA) patients. It also found a higher proportion of NHW patients amongst those who were diagnosed with advanced stage disease and were overweight or obese compared to AA patients. This data suggests that in our patient population, Non-Hispanic White women who were overweight or obese at the time of diagnosis of early onset breast cancer (≤ 45 years old) were more likely to be diagnosed with advanced stage disease than women in other demographic groups. It is possible that this discrepancy is related to racial variations in receptor status. Further investigation is required to correlate these associations in clinical practice with other known demographic variables and disease-specific risk factors in order to better understand how they impact the diagnosis and prognosis of early-onset breast cancer. Citation Format: Austin Kordic, Amanda Reyes, Nadia Ashai. Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-42.

Editorial Commentary.

No AccessUrology PracticeHealth Policy1 Mar 2023Editorial CommentaryThis article comments on the following:Postoperative Opioid Prescribing Following Outpatient Male Urethral Surgery: Evidence for Changeis a letter which has replyReply by Authors Nathan M. Shaw and Lindsay A. Hampson Nathan M. ShawNathan M. Shaw MedStar Georgetown University Hospital, Washington, DC More articles by this author and Lindsay A. HampsonLindsay A. Hampson University of California, San Francisco, California More articles by this author View All Author Informationhttps://doi.org/10.1097/UPJ.0000000000000369.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Commentary." Urology Practice, 10(2), pp. 144–145

The Efficacy and Safety of SARS-CoV-2 Vaccinations in People with Multiple Sclerosis

While people with multiple sclerosis (MS) are not more likely to contract COVID-19, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related complications may be higher for people with MS who have comorbidities or who are taking certain disease modifying therapies (DMT). Robert Shin, Professor of Neurology at MedStar Georgetown University Hospital, Washington, D.C., USA, and Deborah Fuller, Department of Microbiology, University of Washington School of Medicine, and Associate Director of the Washington National Primate Research Center, Seattle, Washington, USA, first discussed why vaccinations against SARS-CoV-2 should be recommended to people with MS. They then discussed evidence that suggests that the antibody response following vaccination may be dampened in people taking some DMTs, especially those that deplete CD20+ B cells; however, T cell responses to vaccinations may also provide protection. There is also evidence that messenger RNA (mRNA) SARS-CoV-2 vaccines, as opposed to viral vector or recombinant protein subunit vaccines, and boosters may lead to a better antibody response. Vaccine responses vary between patients taking different sphinogosine-1-phosphate (S1P) receptor modulators, being low for fingolimod and high for next generation S1P receptor modulators. Overall, more studies of vaccine response and timing are needed to best update the guidelines for people with MS.

Understanding Hypercoagulability with Nephrotic Syndrome: How the Clot Thickens.

Division of Nephrology and Hypertension, MedStar Georgetown University Hospital, Washington, DC Correspondence: Prof. Michael J. Choi, Division of Nephrology and Hypertension, MedStar Georgetown University Hospital, 3800 Reservoir Rd., NW, 6 PHC, Suite F6003, Washington, DC 20007. Email: [email protected] See related article, “Exploring the Role of Antithrombin in Nephrotic Syndrome–Associated Hypercoagulopathy: A Multi-Cohort Study and Meta-Analysis,” on pages 234–244.

S121 Ozanimod in Ulcerative Colitis: A Tertiary Care Center’s Experience Over One Year

Background: It is estimated that the prevalence of ulcerative colitis (UC) in the United States is 465 per 100,000 people, with its incidence projected to increase further in the upcoming years. Although the advent of biologics has revolutionized UC therapeutics, a substantial proportion of patients suffer from refractory disease. Ozanimod is an oral sphingosine-1-phosphate receptor modulator that has been recently approved by the US Food and Drug Administration for moderate to severe UC therapy. Real-world experience with ozanimod in UC remains to be defined. The aim of this study is to evaluate the safety and efficacy of ozanimod in patients with UC at a tertiary medical center. Methods: We performed a retrospective chart review of patients with UC treated with ozanimod within the MedStar health system between June 2021 to June 2022. The following inclusion criteria were applied: individuals 18 years or older, histological diagnosis of UC, and initiated on ozanimod at a MedStar Gastroenterology site. Results: Eight patients with UC (mean age = 35.5 years; 50% women; mean disease duration = 12.4 years; 63 percent pancolitis, 25 percent proctosigmoiditis, 13 percent left-sided colitis) were identified and included in this study, all of whom were seen at MedStar Georgetown University Hospital. Baseline disease characteristics: mean Mayo Endoscopic Score = 2.4, mean CRP = 9.8 μg/g, and mean Fecal Calprotectin = 1276 μg/g. All patients had previously failed treatment with at least one biologic agent. Following ozanimod initiation, one patient entered clinical remission, 3 patients showed improvement in UC symptoms, 3 patients showed no improvement or worsening of UC symptoms (including one who had total colectomy within 10 days of initiation), and one patient discontinued ozanimod use due to relocating abroad. After a mean follow-up time of 4 months post-ozanimod initiation, patients had the following disease characteristics: mean CRP = 14.4 μg/g, and mean Fecal Calprotectin = 912.5 μg/g. Patients treated with ozanimod reported adverse events such as fatigue (n = 4), eye irritation (n = 3), joint pain (n = 2), nausea and vomiting (n = 2), shortness of breath (n = 1), chest pain (n = 1), and brain fog (n = 1). One patient discontinued ozanimod due to adverse events potentially related to ozanimod. Conclusion(s): Ozanimod is well-tolerated with minimal side effects in patients with UC. The overall clinical response to ozanimod was variable; however, most patients experienced improvement in UC symptoms. Considering that all patients had previously failed at least one biologic therapy, our experience indicates that ozanimod is effective in improving symptoms and inducing remission in patients with refractory disease. Future studies with a larger sample and extended follow-up period are warranted to define the efficacy and time to remission of ozanimod in UC patients.

Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost

Background Autologous hematopoietic stem cell transplant (ASCT) remains a cornerstone of therapy for eligible patients with multiple myeloma (MM) and can be incorporated as part of the initial therapy (early ASCT) or at the time of first relapse (delayed ASCT) [1]. Current guidelines recommend that adequate hematopoietic stem cells (HSC should be collected for a potential second ASCT, with a minimum goal of 2 million CD34+ cells/kg per transplant [2]. The stored HSC may be used for either a planned tandem transplant or future salvage ASCT. Less commonly, the previously stored HSC may be used for stem cell "boosts” following either dose intensive, non-myeloablative chemotherapy or for patients with "burned out” bone marrows secondary to extensive prior therapies. [3]. To our knowledge, there is a paucity of data on the effectiveness and survival outcome of patients with multiple relapsed MM who receive a stem cell boost following dose intensive chemotherapy. This study analyzes the clinical outcomes of multiply relapsed MM patients receiving multi-agent chemotherapy followed by a stem cell boost. Outcomes evaluated were overall response rate, proportion of patients who received a subsequent line of therapy, and overall survival. Methods This is a retrospective chart review performed at 2 institutions (Hackensack University Medical Center and MedStar Georgetown University Hospital). Fifty-nine (59) patients with MM aged ≥18 years old who underwent first ASCT from 1999 to 2021 and who collected sufficient s to allow for either tandem or salvage transplant or potential future stem cell boost were included in this study. Response to therapy was defined as stable disease or better on evaluation 1 month following stem cell boost. Patients who received another line of therapy less than 1 month post boost but did not have evidence of disease progression at that time, were excluded from ORR analysis. Overall survival (OS) was defined as the time from stem cell boost to date of death or last follow up. Statistical analysis was performed using STATA v16.0 (Stata Corp, TX, USA). Survival analysis was carried out using the Kaplan-Meier method and the log-rank test was used to compare survival curves. Results The patient characteristics who received a stem cell boost are shown in Table 1 (n=59): male gender (61 %), median age at diagnosis was 60 (range 37-81), median number of lines of therapy 6.3 5 Range 1-16). The patient who received only 1 prior line of therapy had aggressive relapse less than 100 days post melphalan-conditioned ASCT which necessitated use of urgent dose intensive chemotherapy. The stem cell dose used for the boost ASCT ranged from 0.4 to 9.8 X 10^6 CD34+ cells/kg (median 2.3). 1.6. Of the 49 evaluable patients, 28 (57.1%) had response to therapy 1 month post stem cell boost. Overall, 37 (62.7%) patients successfully received a subsequent line of therapy post stem cell boost. The median overall survival for the entire cohort was 129 days (range 1 - 1462 days) (Figure 1). OS was significantly longer in responding patients compared to those who did not respond (182 days vs 82 days, p=0.0081). Conclusions Dose intensive, non-myeloablative chemotherapy can improve survival in heavily pretreated, usually penta-refractory MM that require disease for refractory relapse. The administration of a stem cell boost utilizing previously collected HSCs may assist with hematopoietic recovery following dose intensive chemotherapy and in this subset of patients who have poor marrow reserve from prior therapy. This study serves to demonstrate the clinical outcomes of patients treated with multiagent chemotherapy followed by a stem cell boost. With an ORR of 57.1%, this approach can be effective in the appropriate clinical setting and significantly improves OS in patients who do respond to therapy (Figure 2). The goal of such therapy is to achieve disease control, and often serves as a "bridge” for patients to receive subsequent myeloma-directed therapy that may not be readily available at the time of relapse, such as clinical trial or chimeric antigen receptor T-cell (CAR-T) therapy. This data allows for treating oncologists to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of treating such patients with dose intensive multiagent chemotherapy followed by a stem cell boost.