Mayo Clinic Rochester Research Articles

Editorial introductions.

Editorial introductions.

Measuring Success of Patient Safety Initiatives: The 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade

Measuring Success of Patient Safety Initiatives: The 2023 American Society of Anesthesiologists Practice Guidelines for Monitoring and Antagonism of Neuromuscular Blockade

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Deep Brain Stimulator Device Infection: The Mayo Clinic Rochester Experience.

Deep brain stimulator (DBS)-related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9-6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Outcomes of Older Adults with Non-Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation: A Mayo Clinic Cohort Analysis

Autologous stem cell transplantation (ASCT) is an important treatment that can offer a cure for patients with lymphoma. However, advanced age is an important factor that determines eligibility and outcomes after ASCT. Over the past decade, attributed to improved supportive care, ASCT for older patients has become more feasible. In this study, we report the single-center outcomes of older patients with lymphoma undergoing ASCT at Mayo Clinic Rochester to highlight its interval improvement over time and to help redefine the implications of ASCT in the chimeric antigen receptor T cell therapy era. This single-center retrospective study evaluated the characteristics and outcomes of older patients with lymphoma who underwent ASCT between 2000 and 2021. We report various relevant transplantation-related outcomes, including progression-free survival, overall survival (OS), relapse incidence, and nonrelapse mortality (NRM) in older patients with various lymphoma histologic subtypes. The main outcome was NRM, defined as the time from ASCT to non-lymphoma-related death, with relapse as a competing event. Of 492 patients age ≥65 years were analyzed. The median age at ASCT was 68.8 years. The most common indication for ASCT was diffuse large B cell lymphoma, accounting for 59.3% of cases. In multivariate analyses, patients undergoing ASCT in 2009 to 2021, an Eastern Cooperative Oncology Group Performance Status of 0, and low Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) (0 to 3) had a significantly lower NRM. Factors associated with OS included age, lactate dehydrogenase level, and HCT-CI. The 1-year NRM in older patients was low at 6.0%, in concordance with previous reports. Age should not be the sole factor determining a patient's ASCT eligibility. With the proper patient selection, ASCT remains a reasonable option for older patients with lymphoma.

Financial hardship in breast cancer survivors: a prospective analysis of change in financial concerns over time.

Medical financial hardship, encompassing material, behavioral, and psychologic domains, has been shown to impair quality of life during and after cancer therapy. We sought to evaluate the change in financial concerns in breast cancer survivors over time and identify those at risk of worsening financial concerns. In Mayo Clinic Breast Disease Registry (MCBDR), a prospective cohort of consenting patients seen at Mayo Clinic Rochester within 1 year of their initial breast cancer diagnosis, consenting participants were asked to complete baseline and annual follow-up surveys that included an item on which respondents were asked to report their financial concerns on a linear analogue scale from 0 ("none") to 10 ("constant concerns"). We compared patient-reported financial concern at baseline to that on each patient's most recent survey, with worsening concerns defined as a 1+-point increase. Logistic regression analysis evaluated for possible predictors of worsening financial concerns. One-thousand nine-hundred fifty-seven participants responded to financial concern questions on the baseline and at least one follow-up survey between 2015 and 2020. Three-hundred fifty-seven (18.2%) reported worsening financial concerns. Only baseline financial situation of "enough to pay the bills, but little spare money to buy extra or special things," was associated with a greater likelihood of worsening financial concerns. More than one in seven breast cancer survivors develop worsening financial concerns within 5 years of diagnosis, and those with less financial security at baseline appear to be most vulnerable. Financial concerns may worsen over time for breast cancer survivors, and therefore, oncology providers must continue to assess the financial well-being of survivors over time.

1816. Bloodstream Infection Following Arterial Aneurysm Repair: A Population-Based Study

Abstract Background Bloodstream infection (BSI) following arterial aneurysm repair may signify vascular graft infection (VGI). The incidence of BSI and its implications in patients with arterial grafts have received scant attention with limited contemporary study. Therefore, the aim of the current investigation is to describe the incidence and epidemiology of BSI following arterial aneurysm repair in a population-based cohort. Methods Retrospective case-cohort study using the expanded Rochester Epidemiology Project (e-REP) to identify all arterial aneurysm repairs performed in adults (>18 years) residing in eight counties in southern Minnesota between January 1, 2010 and December 31, 2020. All repairs were performed at Mayo Clinic Rochester. Electronic health records were screened for initial BSI episode following aneurysm repair and complicating VGI. Results Overall, 643 patients underwent 708 aneurysm repairs: 417 endovascular and 291 open surgical repairs. Forty-two patients developed BSI during 2,992 cumulative person-years of follow-up. The median time from repair to BSI was 3.1 [interquartile range 0.5, 6.4] years. The BSI incidence rate, in cases per 1000 person-years, was 14.0 (95% CI 10.1-19.0) overall, including 18.2 (95% CI 11.9-26.7) following open surgical repair and 10.2 (95% CI 5.8-16.6) following endovascular repair (p=0.148). Thirty-nine (92.9%) of the BSI cases were monomicrobial, with 18 (46.2%) due to Gram-positive organisms and 21 (53.8%) due to Gram-negative organisms. Of the 42 patients with BSI, 10 (23.8%) had VGI. VGI occurred in 8/18 (44.4%) monomicrobial Gram-positive BSI as compared to 2/21 (9.5%) monomicrobial Gram-negative BSI (p=0.013). The 3-year mortality rate following BSI was 52.3%. Conclusion There was no statistically significant difference in incidence rates of BSI following open surgical repair and endovascular repair. Higher rates of VGI were seen with Gram-positive BSI as compared to Gram-negative BSI. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties.

Inherited myopathy plus: Double-trouble from rare neuromuscular disorders

A rare disorder in the USA is one that affects <200,000 people, making inherited myopathies rare diseases. Increasing access to genetic testing has been instrumental for the diagnosis of inherited myopathies. Genetic findings, however, require clinical correlation due to variable phenotype, polygenic etiology of certain inherited disorders, and possible co-existing independent neuromuscular disorders. We searched the Mayo Clinic Rochester medical record (2004–2020) to identify adult patients carrying pathogenic variants or likely pathogenic variants in genes causative of myopathies and having a coexisting independent neuromuscular disorder classified as rare at https://rarediseases.info.nih.gov/. One additional patient was identified at Nationwide Children's hospital. Clinical and laboratory findings were reviewed. We identified 14 patients from 13 families fulfilling search criteria. Seven patients had a “double-trouble” inherited myopathy; two had an inherited myopathy with coexistent idiopathic myositis; three had an inherited myopathy with coexisting rare neuromuscular disorder of neurogenic type; a female DMD carrier had co-existing distal spinal muscular atrophy, which was featuring the clinical phenotype; and a patient with a MYH7 pathogenic variant had Sandhoff disease causing motor neuron disease. These cases highlight the relevance of correlating genetic findings, even when diagnostic, with clinical features, to allow precise diagnosis, optimal care, and accurate prognosis.

Deciphering the clinico‐radiological heterogeneity of dysexecutive Alzheimer’s disease using unsupervised machine learning techniques

AbstractBackgroundDysexecutive Alzheimer's disease (dAD) is a relatively early‐onset variant of AD primarily degrading core executive functions in the absence of predominant behavioral symptoms. Clinical observations suggest substantial variability in clinical, cognitive and neuroimaging profiles within this syndrome. In this presentation, we will discuss our ongoing work disentangling this heterogeneity using unsupervised machine learning techniques.MethodWe collected clinical, neuropsychological and multimodal imaging (MRI, FDG‐PET, amyloid‐PET, tau‐PET) data on 52 dAD patients assessed in our behavioral neurology clinic at Mayo Clinic Rochester. We first performed a spectral clustering analysis based on FDG‐PET to delineate latent patterns of network degeneration (referred as “eigenbrains”) and assessed the relationships between these eigenbrains and clinical and cognitive symptomatology. We then performed a hierarchical clustering on these eigenbrains to derive data‐driven subtypes of dAD. We compared clinical and cognitive data between subtypes, and then compared the imaging profiles to 52 amyloid‐negative age‐ and sex‐matched controls.ResultSix eigenbrains explained approximatively 48% of the variance in FDG‐PET patterns and primarily reflected heteromodal to primary motor/sensory, left‐right hemispheric asymmetry, and anterior‐to‐posterior gradients of macro‐scale cortical organization (Fig 1). These eigenbrains differentially related to reported age at symptom onset, degree of clinical impairment, and performance on a wide range of cognitive domains (executive functions, episodic memory, and visuospatial). Hierarchical clustering revealed four dAD subtypes (diffuse, biparietal, left‐hemisphere, right‐hemisphere). These subtypes differed in reported age at symptom onset and cognitive profile, where the heteromodal‐diffuse subtype exhibited an overall worse clinical picture and the biparietal had a milder profile compared to other subtypes, which was not explained by disease duration. Additionally, spatial patterns of tau distribution and neurodegeneration overlapped with patterns of FDG‐PET hypometabolism in each subtype, whereas patterns of amyloid deposition were similar across subtypes (Figs 2 &amp; 3).ConclusionAlmost half of the variance in macro‐scale patterns of hypometabolism in this dAD cohort was accounted for by six eigenbrains. These eigenbrains captured the inter‐individual variability in age at symptom onset and cognitive impairment. Four dAD subtypes derived from these eigenbrains revealed meaningful differences in clinical, cognitive, and imaging profiles. Recognizing this heterogeneity has significant clinical implications for diagnosis, prognosis, and symptom monitoring.

Causes of Early Mortality After Transvenous Lead Removal.

Recognition of the causes of early mortality (≤30days) after transvenous lead removal (TLR) is an essential step for the development of quality improvement programs. This study sought to determine the causes of early mortality after TLR and to further understand the circumstances surrounding death after TLR. A retrospective analysis was performed of all patients undergoing TLR from January 1, 2001, to January 1, 2021, at the Mayo Clinic (Rochester, Minnesota; Phoenix, Arizona; and Jacksonville, Florida). Causes of death were identified through a detailed chart review of the electronic health record from within the Mayo Clinic system and outside records when available. The causes of death were further characterized based on whether it was related to the TLR procedure. A total of 2,319 patients were included in the study. The overall 30-day all-cause mortality rate was 3% (n=69). Among all 30-day deaths, infection was the most common primary cause of death (42%). This was followed by decompensated heart failure (17%), procedure-related death (10%), sudden cardiac arrest (7%), and respiratory failure (6%). The 30-day mortality rate directly due to complications associated with the TLR procedure was 0.3%. One-third of deaths (33%) occurred after discharge from the index hospitalization; among these, 43% were readmitted before their death, 35% died at home or at a nursing facility, and 22% were discharged on comfort care and died in hospice. The main reasons for readmission before death were sepsis and decompensated heart failure. The majority (90%) of 30-day mortality after TLR was not due to complications associated with TLR procedures. The primary causes were infection and decompensated heart failure. This highlights the importance of increased emphasis on postprocedure management of infection and heart failure to reduce postoperative mortality, including after hospital discharge.

Minimally Invasive Compared With Open Surgery in High-Risk Endometrial Cancer: A Systematic Review and Meta-analysis.

To compare outcomes between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer. A cohort study of all patients who underwent surgery for high-risk endometrial cancer between 1999 and 2016 at Mayo Clinic (Rochester, Minnesota) and a literature search of MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and Scopus of all published studies until December 2020. The systematic review identified 2,332 patients (14 studies, all retrospective except a subanalysis of a randomized comparison) and the cohort study identified 542 additional patients. Articles were included if reporting original data on overall survival and disease-free survival among patients with high-risk endometrial cancer, defined as International Federation of Gynecology and Obstetrics grade 3 endometrioid, serous, clear cell, mixed histology, or uterine carcinosarcoma. Studies that did not report at least one of the main outcomes, those in which one surgical technique (robotic or laparoscopic surgery) was missing in the comparison analysis with open surgery, and case reports were excluded. Additional data were extracted from a retrospective cohort of patients from Mayo. A random-effect model was used for meta-analysis. This systematic review and meta-analysis was registered in PROSPERO. Literature search and data extraction were performed independently by two reviewers, as well as quality assessment using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and the Newcastle-Ottawa Scale. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Meta-analysis showed that disease-free survival and overall survival in patients with high-risk endometrial cancer who underwent minimally invasive surgery were not statistically different from those of patients who underwent open abdominal surgery (relative risk [RR] 0.93, 95% CI 0.82-1.05, I2 20%, P=.23; and RR 0.92, 95% CI 0.77-1.11, I2 31%, P=.12, respectively). Subgroup analysis by stage (early vs advanced) did not identify a difference between surgical approaches. Minimally invasive surgery and open surgery had similar disease-free survival and overall survival in patients with high-risk endometrial cancer. PROSPERO, CRD42021275535.

Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia with TP53 Mutations

Background: Aberration of the TP53 gene in chronic lymphocytic leukemia (CLL) is a well-established marker of poor prognosis and a predictor of chemorefractory disease. Identification of a TP53 gene mutation is clinically useful in determining which patients may benefit from small-molecule inhibitors such as Bruton tyrosine kinase (BTKi) and BCL2 inhibitors (BCL2i). However, the treatment patterns in routine practice and outcomes of patients harboring TP53 mutations in CLL is not well reported. We present a descriptive analysis of CLL patients treated at Mayo Clinic with TP53 mutations including their demographics, treatment patterns, and outcomes. Methods: Patients with CLL who had a TP53 mutation detected by Sanger sequencing between June 2014 and April 2021 at Mayo Clinic Rochester were identified from a hematopathology database. Patient demographics, clinical and pathologic characteristics, treatment, and follow-up information were abstracted from the Mayo Clinic CLL database and by chart review. Date of TP53 mutation test was baseline. Discrete variables were compared using Chi-square or Fisher's exact tests; continuous variables were compared using Kruskal-Wallis test. Overall survival (OS) was calculated from date of TP53 mutation test until date of death from any cause or last known date alive. Rates of Richter transformation (RT) by prior treatment exposure were estimated by cumulative incidence accounting for competing risk of death. Results: A total of 145 patients were identified; 70% were male, and the median age at diagnosis was 59 years (range: 36-92). At diagnosis, 15% of patients had Rai stage III-IV, 77% had unmutated IGHV, 38% had del17p, 92% had high or very high CLL-IPI, and 62% had ≥3 cytogenetic abnormalities (Table 1). A TP53 gene mutation was identified prior to any CLL treatment in 63 patients (43%, Group 1) and after at least one prior line of treatment in 82 patients (57%, Group 2). The median time from CLL diagnosis to the first detected TP53 mutation was 3 months in Group 1 and 96 months in Group 2. There was significant heterogeneity in types of TP53 mutations with the majority of variants (n=102) being unique to an individual. At the time of TP53 mutation detection, Group 2 patients more frequently had advanced Rai stage and unmutated IGHV status (Table 1). Del17p by FISH was present prior to or at time of TP53 mutation identification (+/- 3 months) in 54% of patients in Group 1 and 52% in Group 2. Group 1 had a median follow-up of 26 months (from TP53 mutation detection date); 46/63 patients had initiated a first-line (1L) treatment (39 BTKi-based, 1 BCL2i-based, 2 BTKi+BCL2i-based, 4 chemoimmunotherapy [CIT]). In Group 2, the median number of prior lines of therapy was 2 (range 1-16). Prior treatment exposure included 38 (46%) CIT only, 41 (50%) BTKi-based ± CIT, and 3 (4%) BTKi-based + BCL2i-based ± CIT. Median follow-up was 21 months; 56/82 patients had initiated a new line of therapy (subsequent 1L). For 38 patients with prior CIT only exposure, 28 had subsequent 1L including 21 BTKi-based, 2 BCL2i-based, and 5 CIT. For 44 patients with prior BTKi exposure, 28 had subsequent 1L including 5 BTKi-based, 5 BCL2i-based, 9 BTKi+BCL2i-based, and 9 CIT. The median OS was not reached in Group 1 and was 40.6 months (95% CI 30.1-NE) in Group 2 (HR=0.21, 95% CI=0.10-0.45) (Figure 1). In Group 2, the median OS for patients with prior CIT only exposure was 55.5 (95% CI 30.1-NE) months and for patients with prior BTKi exposure was 33.3 (95% CI 14.7-NE) months (HR=0.59, 95% CI=0.31-1.12) (Figure 1). Three patients in Group 1 and 13 patients in Group 2 (3 prior CIT only, 10 prior BTKi) developed RT during the follow-up period; the cumulative incidence rates of RT at 2- and 5-year were 1.7% and 4.6%, respectively, in Group 1, and 10.8% and 21.0%, respectively, in Group 2. Conclusions: Regardless of prior treatment exposure, enrichment for high-risk features was present at time of TP53 mutation detection. Majority of patients were treated with novel agents after known TP53 mutations. OS after TP53 mutation was inferior in patients who had been previously treated, particularly those who had BTKi exposure already prior to TP53 mutation detection, compared to previously untreated patients. Future studies are needed to understand the characteristics of clonal evolution before and after treatment and the clinical impact of specific TP53 mutations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Persistance or Reappearance of Serum Monoclonal Protein Detected By Mass Spectrometry Is a Major Prognostic Factor in Patients with Newly Diagnosed Multiple Myeloma

Introduction: Durability of minimal residual disease (MRD) based on bone marrow examination is associated with a progression-free survival (PFS) benefit when it is undetected for >6-12 months. However, MRD assessment is limited by the heterogeneous involvement of bone marrow and invasive nature of the procedure. In contrast, Mass-Fix is a mass spectrometry based blood test that can detect small amounts of monoclonal protein. Herein, we hypothesize that achieving sustained Mass-Fix negativity for at least 6 or 12 months, improves outcomes compared to patients with nonsustained Mass-Fix negativity. In addition, we assess the clinical outcome of patients with loss of Mass-Fix negativity. Methods: This retrospective cohort study included consecutive patients seen at Mayo Clinic Rochester with newly diagnosed multiple myeloma (MM). Patients achieving at least very good partial response, and who had serial Mass-Fix testing every 6-12 months were included in this study. MRD in bone marrow aspirate was measured by flow cytometry (threshold 1 tumor cell/105 white blood cells). The Kaplan Meier or Simon-Makuch methods were used to graph the survival function. Progression-free survival was defined from diagnosis or the landmark point (2 years after diagnosis) to progression or death from any cause. Results: We identified 443 patients with NDMM, between May 1, 2017 and May 31, 2020. Among these, 274 patients had marrow MRD examination during their follow-up. With a median follow-up of 41 months from diagnosis, 56% of patients achieved Mass-Fix negativity, 43% marrow MRD negativity, and 23% achieved both Mass-Fix and MRD negativity. Most patients received a bortezomib-lenalidomide-dexamethasone induction followed by autologous transplantation (73%). In a 2 year landmark analysis, patients achieving Mass-Fix negativity had a better PFS at 2-years from landmark (4 years from diagnosis) than patients who did not (86.7% vs. 70.0% , p<0.001). Similarly, in a landmark analysis, patients with negative marrow MRD had a better PFS than those with positive MRD (88.1% vs. 62.5%, p=0.027). However, overall survival was similar between patients achieving Mass-Fix or MRD negativity and those who did not. In patients with Mass-Fix negativity, 76% and 71% achieved sustained Mass-Fix negativity for ≥6 and ≥12 months, respectively. In a landmark analysis, a significant difference in 2-year PFS was observed between patients with sustained Mass-Fix negativity ≥6 months and < 6 months (94.1% vs. 78.9%, p=0.013, Figure 1A). Patients with sustained Mass-Fix negativity≥12 months and < 12 months had a better 2-year PFS in a landmark analysis (94.4 vs. 80.2, p=0.019). Similarly, in a landmark analysis, patients with sustained marrow MRD negativity for ≥12 months had a better 2-year PFS from the landmark (4 years from diagnosis) than patients with MRD negativity for <12 months (91.8% vs. 72.8%, p<0.001). Patients achieving both sustained Mass-Fix and marrow negativity for ≥6 months had a better 2-year PFS from the landmark than patients who did not in a landmark analysis (91.5% vs. 73.1%, p=0.001). In our cohort, 33% of patients achieving Mass-Fix negativity had a subsequent loss of Mass-Fix negativity by 4 years; median duration of Mass-Fix negativity was 27 months (95% CI 25-30 months). Nearly half of patients with loss of Mass-Fix negativity (39/81) had eventually progressive disease (PD) according to IMWG criteria. In a 2-year landmark analysis, 2-year PFS (4 years from diagnosis) was better in patients with ≥2 consecutive negative Mass-Fix than in patients with loss of Mass-Fix negativity (88.1% vs. 68.6%, p<0.001, Figure 1B). Patients with loss of Mass-Fix negativity after the first year following diagnosis had a better 2-year overall survival than patients with conversion before 1 year in a landmark analysis (100.0% vs. 90.6%, p=0.045). Finally, patients who achieved sustained Mass-Fix negativity for ≥6 months had a better 4-year PFS than patients with loss of sustained Mass-Fix negativity with Simon-Makuch method (94.0% vs. 28%, p<0.001). Conclusions: In summary, this study demonstrates that sustained Mass-Fix negativity may represent a robust evaluation of prognosis and disease control. Moreover, loss of Mass-Fix negativity is associated with a worse outcome and could be used as a marker for earlier treatment interventions in MM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes of Allogeneic Stem Cell Transplant for Multiple Myeloma

Background Allogeneic stem cell transplant (allo-SCT) for treatment of multiple myeloma (MM) is controversial. For some, allo-SCT may drive treatment-resistant disease into remission through a graft vs myeloma effect. For others, it incurs considerable morbidity from opportunistic infections and graft vs host effects. Allo-SCT usage for MM has increased over the past 25 years despite mixed efficacy and the absence of clear treatment guidelines. We aimed to determine the natural history of patients who underwent an allo-SCT following an autologous stem cell transplant (ASCT) and identify characteristics associated with outcome. Methods We retrospectively analyzed 89 patients diagnosed with multiple myeloma who had received an allo-SCT following an ASCT between 2000 and 2022 at Mayo Clinic Rochester. Patient data were obtained from the Mayo Clinic Transplant Center Database and our institution's electronic medical records. Overall survival (OS) and progression free survival (PFS) were calculated as time from allo-SCT to death from any cause and first observation of relapse or death, respectively. OS and PFS rates were estimated using the Kaplan-Meier method. P < 0.05 was considered statistically significant. Results The cohort is characterized as follows: median patient age of 51.3 years, 71% male, 90% white/Caucasian. Indication for allo-SCT were 91.0% (N=81) relapsed/progressive disease, 9.0% (N=8) high risk in remission. Cytogenetic risk stratification at diagnosis was available for 94% of patients (N=84) with 63% (N=56) standard risk, 32% (N=28) high risk according to International Myeloma Working Group criteria. By conditioning regimen, 55% (N=49) underwent full myeloablative allo, 45% (N=40) non-myeloablative (mini)-allo. Median follow-up, OS, and PFS was 11.5, 1.7, and 0.8 years, respectively (Table 1). OS was 46% (N=41) at 2 years, 26% (N=21) at 4 years, and 16% (N=14) at 8 years (Figure 1). Outcome was not significantly impacted by age, sex, race, indication for allo-SCT, or myeloablative regimen. Patient cytogenetic risk at diagnosis approached, but did not reach, statistical significance (p=0.22) with overall survival of high-risk patients being 32% (N=9), 18% (N=5), and 7.1% (N=2) at 2, 4, and 8 years, respectively, compared to 52% (N=29), 27% (N=15), and 20% (N=11) over the same times in standard risk. PFS was 27% (N=24) at 2 years follow-up, 16% (N=14) at 4 years, and 7.9% (N=7) at 8 years (Figure 1). This did not vary significantly by age, race, indication for allo-SCT, cytogenetic risk, or conditioning regimen. Sex approached, but did not reach, statistical significance (p=0.16) with progression-free survival of females being 19% (N=5), 15% (N=4), and 7.7% (N=1) at 2, 4, and 8 years follow-up, respectively, compared to males at 30% (N=19), 16% (N=10), and 9.5% (N=6) over the same times. Discussion Long-term survival was achieved in less than 20% of patients who underwent allo-SCT following an ASCT. Nearly 75% of patients experienced disease progression or death by 2 years. This suggests minimal benefit to the use of allo-SCT as treatment for multiple myeloma outside of select patients. Novel therapeutics such as chimeric antigen receptor T cells (CAR-T) or bispecific T-cell engager (BiTE) should be considered as an alternative. Subsequent studies will further examine patient characteristics and associated outcomes to determine the population best suited for allo-SCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prognosis Score for Overall Survival with CAR-T Therapy in Aggressive Lymphoma

Background: Since 2017, six chimeric antigen receptor T cell (CAR-T) therapies have been approved by the FDA for hematologic malignancies. Despite the transformative potential of this therapy, more tools to assist with identifying patients with increased likelihood of benefitting from this therapy will be helpful, particularly given the logistical complexity and socio-economic demands for CAR-T relative to other therapies. Health care resource restriction during the COVID-19 pandemic highlights the need for these tools. We present a simple survival score that uses 3 readily available clinical labs: platelet (plt), absolute lymphocyte count (ALC), and Lactate dehydrogenase (LDH) to predict the risk of dying within 6 months of CAR-T therapy in patients with aggressive lymphoma. Methods: We conducted a retrospective chart review of patients with aggressive non-Hodgkin lymphoma (NHL) who received FDA-approved CAR-T between Jan 2018 to Jan 2022 at Mayo Clinic Rochester. Demographics and lab variables were selected based on univariate analysis for clinical and statistical significance and tested in a multivariate logistic regression model. Bootstrapping test was used to test the accuracy of the model to predict for death within 6 months of CAR-T infusion. Patients were scored based on the model, and Kaplan-Meier curve for overall survival (OS) based on the score was plotted. Results: Among a total of 110 pts who received CAR-T, 27 (25%) pts died within the first 6 months post CAR-T infusion (OS ≤ 6 mo). Disease progression was the main cause of death (18/25, 72%), followed by infection (4/25, 16%), CAR-T related (HLH/MAS, 2/25, 8%), second primary malignancy (1/25, 4%) and unknown (2/25, 8%).Baseline demographics were comparable between the OS>6mo and ≤6months groups (Table 1). Patients’ ECOG, Karnofsky performance status and 11 labs at the time of evaluation for CAR-T therapy (initial eligibility assessment, prior to leukapheresis) were compared between those who died from any cause within 6 months of CAR-T infusion and those who did not. Hemoglobin, plt, ALC, absolute monocyte count, C- Reactive Protein, ferritin, and LDH were selected as clinically and/or statistically significant variables for multivariate testing. Multivariate regression with boot-strap testing identified plt, ALC, and LDH as the most predictive variables with 80.9 ± 11.7% accuracy for predicting death within 6 months of CAR-T infusion. Patients were scored 0-3 using these 3 labs, with 1 point assigned for plt ≤ 100 X109/L, ALC ≤ 0.4 X109/L, or LDH > 222 U/L (upper limit of normal). OS by this survival score is shown in Figure 1. Discussion: Due to the curative potential of CAR-T, patients with broader characteristics than those treated on registration studies have been treated in standard of care practice. While an estimated 5%-10% risk of CAR-T associated deaths in the first 3 months is seen across all patients in clinical trials, predictors for early death after CAR-T in real-world patient populations can provide additional context for pts and providers when selecting treatment. This survival score is important proof of concept that a simple model using readily accessible clinical labs at the time of CAR-T evaluation could provide additional context to help with additional clinical decision-making. Multicenter prospective studies will help define and validate the definitive survival scoring system. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Use of Liquid Tranexamic Acid for Pediatric Patients with Bleeding Disorders

Introduction: Antifibrinolytics are widely used in the prevention and treatment of bleeding, they can be used as a monotherapy for mild bleeding/minor procedures and as adjunctive therapy in combination with other hemostatic agents for moderate/severe bleeding and major procedures. Tranexamic acid (TXA) and aminocaproic acid (6-ACA) are the only agents licensed for at-home administration. TXA is available in tablet and intravenous dosage forms, while 6-ACA is available in tablet, oral solution, and intravenous dosage forms. 6-ACA oral solution (AAOS) is the only commercially-available option for those who cannot swallow tablets, however, barriers to its use include insurance denial and high cost/copayment. TXA tablets can be crushed and mixed into an aqueous solution and is stable for up to 31 days3, thus crushing a tablet into water for immediate use should not affect its efficacy. We report our experience using crushed tranexamic acid tablets in water (cTXAw) in young patients with bleeding disorders. Methods: In this single-center, IRB-exempt retrospective chart review at Mayo Clinic Rochester, MN eligible patients were less than 10 years of age and who had been prescribed any formulation of TXA from December 2018 to July 2022. For patients prescribed cTXAw, data collection included age, sex, TXA dose, indication for use, clinical outcome, and side effects attributed to cTXAw. Bleeding outcomes were defined as major, clinically relevant non-major, and minor bleeding according to ISTH criteria. To create the cTXAw, a TXA 650 mg tablet was crushed and dissolved in 10 ml water resulting in a 65 mg/ml solution. Once dissolved, patients/caregivers were instructed to immediately draw up and administer the appropriate weight-based dose and then discard the excess cTXAw. The procedure was repeated with each dose. Results: Our electronic medical record search identified 666 patients who received TXA of whom 32 were prescribed cTXAw, of whom 7 were prescribed tranexamic acid to be used on as needed basis and it was not used. The remaining 25 had documented use of the medication (table 1); median age was 3 years ( 10 days - 9 years ) and 19 (76%) were male. Bleeding disorders included: von Willebrand disease (52%), hemophilia (20%), Factor VII deficiency (12%), inherited platelet disorders (8%), and immune thrombocytopenia (8%). Twenty-five patients received 32 courses of cTXAw for 21 procedures and 11 bleeding events for a mean duration of 6 days (1 - 14 days). Most patients received 25 mg/kg (28/32, 88%), the rest received 10 mg/kg (4/32, 12%). TXA was used as monotherapy in 24 occasions (75%; 15 procedures and 9 bleeding events) and as adjunctive therapy in 8 (25%; 6 procedures and 2 bleeding events); 6 received factor replacement and 2 received DDAVP. Type of factor and indication included: FVIII for circumcision (n=2), VWF concentrate for tonsillectomy and adenoidectomy (n=2), FVIII for oral bleeding (n=1), VWF concentrate for hypospadias repair (n=1). None of the 21 procedures (5 circumcision, 5 dental procedures, 5 myringotomy tube placement, 3 tonsillectomy and adenoidectomy, 2 endoscopies, 1 hypospadias repair) were complicated by bleeding as defined by ISTH criteria. Out of 11 bleeding events (4 oral bleeding, 4 frequent epistaxis, 2 hematomas, 1 laceration), 9 had effective hemostasis with the use of cTXAw (82%), one had no response (9%; used for recurrent epistaxis in addition to DDAVP), one had no reported outcome (9%). None of the patients reported side effects from using cTXAw. Using tranexamic acid represents a significant cost savings to families and the health care system. The median age of patients in this study was 3 years of age, and the average 3-year-old weighs 14 kg4. Average wholesale price (AWP) for TXA is $5.21 per 650 mg tablet, thus a course of cTXAw at 25 mg/kg/dose (350 mg) every 6 hours for 6 days costs AWP $125. A similar regimen using 6-ACA is 50 mg/kg/dose (700 mg) every 6 hours for 6 days4. The AWP for 6-ACA is $13.47 per mL of the 250 mg/mL oral solution. For the same 3-year-old, a course of therapy of 6-ACA oral solution costs $905. Of our 13 patients who had also been prescribed AAOS before cTXAw, 8 (61.5%) patients were documented as unable to receive the AAOS due to either prohibitive cost or insurance denial. Conclusions: Crushed TXA tablets in water (cTXAw) appears to be effective, safe, and cost-effective for young patients with bleeding disorders. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patients with Monoclonal Gammopathy Have a High Rate of Second Symptomatic COVID-19 Infection Even after a Prior COVID-19 Infection and Vaccination

Background: Patients with hematologic malignancies, including multiple myeloma (MM), light chain (AL) amyloidosis, smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS), have disproportionately high rates of COVID-19 infection and associated mortality. While inferior immune response to COVID-19 vaccination have been described in patients with monoclonal gammopathy, information on the rate and severity of COVID-19 infections in patients who do demonstrate immunogenicity after a prior infection or vaccination is limited. Additionally, the prevalence and clinical course of second symptomatic COVID-19 infections in patients with monoclonal gammopathy is not known. Methods: Patients with MGUS, SMM, MM or AL amyloidosis evaluated at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 were screened. Patients with a positive polymerase chain reaction test for SARS-CoV-2 and either a spike Ab (Ab) or a nucleocapsid Ab tested were included. Spike Ab was reported quantitatively (positive result >0.8 IU/mL per laboratory standard) and nucleocapsid Ab testing was reported as either positive or negative. For this study, we defined "fully vaccinated” as 2 doses of Pfizer or Moderna mRNA vaccine or 1 dose of the Janssen vaccine based on the prevalent CDC recommendation during the study period. Patients with a 2nd symptomatic COVID-19 infection had an interim negative COVID-19 test result with complete clinical recovery. Results: Out of 19,943 patients with an underlying monoclonal gammopathy, 483 patients (2.4%) had a documented positive COVID-19 PCR test and 101 patients had COVID-19 antibody testing performed [spike Ab=54, nucleocapsid Ab=47]. The baseline characteristics of these 101 patients are depicted in Table 1. Out of the 101 patients, 13 (13%) developed a 2nd symptomatic COVID-19 infection. Details of the timeline for second infections in relation to vaccination, antibody testing and ongoing treatment are depicted in Figure 1. The majority of 2nd COVID-19 were mild (11/13, 85%) and the 2 patients (15%) with a severe 2nd infection were both unvaccinated. The median time to 2nd infection was 6.3 months (range 1-19 months) from the 1st COVID-19 infection. Of the 42 patients with MM/AL, 25 patients were in remission and 1 out of these 25 (4%) patients developed a 2nd COVID-19 infection. Compared to patients in remission, 5 (29%) of the 17 patients with MM/AL not in remission developed a 2nd infection (p=0.03). Rate of 2nd infection was 21% (6/28) in unvaccinated patients compared to 10% (7/73) in patients after completion of initial vaccination series (p=0.11). Six out of the 7 vaccinated patients had received a third dose of vaccination prior to the 2nd infection. Among the 382 patients in whom an antibody test was not performed, 22 (6%) patients developed a second infection out of which 3 (14%) were severe. Out of 101 patients, 85 patients were unvaccinated at the time of first infection and 63 (74%) developed a positive COVID-19 Ab after the 1st symptomatic infection (spike Ab n=38, nucleocapsid Ab n=25). Out of these 63 patients with seropositivity, 7 (11%) developed a second symptomatic COVID-19 infection at a median time of 9.9 months (range 2.9-19.6) from first COVID-19 infection and 6 (range 2-18.7) months from the time of antibody testing. To assess seropositivity after vaccination, spike Ab was used as nucleocapsid Ab can be negative after mRNA vaccination. Among the vaccinated patients at the time of first infection (n=16), 6 had a spike Ab tested before 1st COVID-19 infection at a median of 65 (range 16-109) days from vaccination. Of these, 5 (83%) demonstrated a positive spike Ab response to the vaccination. Despite seropositivity, all 5 developed COVID-19 and 2 patients with positive spike Ab developed a severe 1st COVID-19 infection (without mortality) at 84 days and 99 days from vaccination, respectively [spike Ab level was 145 IU/mL and > 250 IU/mL, respectively]. None of the vaccinated and seropositive patients (n=10) developed a 2nd symptomatic COVID-19 infection. Conclusion: Patients with an underlying MM, AL or MGUS demonstrate a substantial risk for second symptomatic COVID-19 infections suggesting a rapidly waning immunity. Most of the 2nd COVID-19 infections were mild, with severe infections restricted to the unvaccinated population. Patients in whom underlying MM or AL was in remission was protective against a 2nd infection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes with Immunochemotherapy Plus Radiation Versus Immunochemotherapy Alone in Stage I Diffuse Large B-Cell Lymphoma: A Retrospective Study

Introduction Diffuse Large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with a prognosis highly dependent on the stage of the disease. The mainstay of front-line therapy for limited-stage DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP-like immunochemotherapy (IC). The impact of combined modality therapy (CMT) with radiation therapy (RT) after IC remains uncertain in the rituximab era. In the pre-rituximab era, studies comparing the efficacy of chemotherapy with or without RT showed heterogenous results. To date, only a few single institutional studies have compared IC versus CMT. The aim of this study is to evaluate the efficacy of standard IC compared to CMT in patients with stage I DLBCL in the rituximab era. Methods Adult patients with stage I DLBCL diagnosed between 2002 to 2015 and seen at Mayo Clinic Rochester were identified. Data were obtained from medical records. All patients were treated with IC (R-CHOP or R-CHOP-like), or IC followed by radiation (CMT). The student's t-test or the Wilcoxon rank-sum test was used to analyze between-group differences, as appropriate. Chi-square or Fisher's exact test was used for categorical variable comparisons. Progression-free survival (PFS) was defined as the time from the date of diagnosis to the date of relapse, death or the date of the last follow-up and was analyzed using the Kaplan-Meier method. Overall survival (OS) was defined as the time from the date of diagnosis to the date of last follow-up or death. Response to treatment was evaluated by treating physicians. Results The study included 123 patients diagnosed with stage I DLBCL with a median follow-up time of 65.9 months for IC arm and 56.2 months for CMT arm. Overall, 78 patients were treated with six cycles of IC, and 45 patients were treated with 2-4 cycles of IC followed by involved-site radiation (2 cycles in 4 patients, 3 cycles in 25 patients, 4 cycles in 16 patients). There were no significant differences in age, sex, or extranodal involvement. In the IC group, 59 patients had cell of origin data available: 44 (56.41%) were GCB subtype and 15 patients (19.23%) were non-GCB subtype. In the CMT group, 21 patients (47%) and 9 patients (20%) had GCB and non-GCB subtypes, respectively. Double-hit lymphoma (defined as rearrangement of MYC together with rearrangement of BCL2 and/or BCL6) was reported in 4 out of 78 patients in the IC arm and 2 out of 45 patients in the CMT arm. There was no significant difference in response rates to frontline treatment between groups. In the IC group, the overall response rate (ORR) was 92% (n=72), and the rate of complete response (CR) was 87% (n=68), partial response (PR) was 5% (N=4), stable disease (SD) was 5% (n=4), and progressive disease (PD) was 5% (n=4). In the CMT group, the ORR was 96% (n=43, all CR); 2 patients achieved SD (4%) and no patients had a PR or PD. With a median follow-up time of 65.9 months for IC arm, 14 patients had died. With a median follow-up of 56.2 months for the CMT arm, 14 patients had died. Median PFS was not reached in the IC group while PFS was more than 10 years in the CMT group (p=0.7851) [Figure 1]. There was no significant OS difference observed in both groups (p=0.2561) [Figure 2]. Conclusion Our study showed no significant difference in OS and PFS between patients with stage I DLBCL treated with IC or CMT. Future research on a larger patient population is needed to evaluate the role of consolidation radiotherapy in early stage DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Artificial Intelligence-Enhanced Models to Predict Light Chain Amyloidosis from Patients with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma

Background: Early diagnosis of AL amyloidosis remains a diagnostic challenge, mainly due to the low prevalence of the disease and heterogeneity of presentation. Artificial intelligence (AI) is a tool which can assist in improving disease recognition. Objective: To establish an AI-based model to accurately discriminate patients with AL amyloidosis from patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), who are at risk of developing AL amyloidosis. Material & Methods: We screened all consecutive patients from the dysproteinemia database at Mayo Clinic Rochester with the diagnoses of MGUS, SMM and AL amyloidosis who were diagnosed between January 1, 2000, and December 31, 2018 and evaluated within 90 days of their diagnosis. Patients who had more than one diagnosis were excluded. The choice of variables to be included in the models were those in whom data was available in >50% of the patients (with one exception being serum free light chain assay which was available in 44% of patients but deemed important for modeling). The variables included in the modeling were the following: Age, gender, height, weight, systolic blood pressure, diastolic blood pressure, heart rate, hemoglobin, MCV, white blood count, absolute lymphocyte count, platelet count, creatinine, albumin, calcium, SGOT, alkaline phosphatase, total bilirubin, serum free kappa and serum free lambda. In a subset model, we incorporated the AI-enhanced electrocardiogram (AI-ECG) score for cardiac amyloidosis (available in routine clinical practice at Mayo Clinic). This variable is AI-based captures from standard 12-lead ECG to predict the probability of cardiac amyloidosis.1 We randomly divided the final study cohort in a 1:1 ratio to training and validation set. Random forest algorithm was used for modeling to predict the probability of AL amyloidosis diagnosis versus non-AL amyloidosis diagnosis (i.e., MGUS/SMM). Results: 20, 579 patients were screened, of which 4,087 patients (19.9%) were included in this study (MGUS n=2716, AL amyloidosis n=1217, SMM n=154). The first model (ALERT 20) included the above-mentioned 20 variables, of which 7 were clinical and 13 were common blood count and blood chemistry testing. The validation set yielded an AUC-ROC of 0.946 for accurate classification of AL amyloidosis against MGUS/SMM. The second model (ALERT 20-ECG model) included all variables used in the ALERT 20 mode plus the AI-ECG score. In this model, 3090 patients were included, after excluding patients with missing ECG (MGUS n=1896, AL amyloidosis n=1075, SMM n=119). By adding the AI-ECG score, the AUC-ROC in the validation set for accurate disease classification increased modestly to 0.958. Analysis of the relative contribution of each variable to model performance identified serum free light chains, serum albumin and AI-ECG as the most influential variables. As disease prevalence decreases the positive predictive value (PPV) and increases the negative predictive value (NPV) of a model, we tested the models’ performance in various prevalence scenarios, including the estimated prevalence of AL amyloidosis among MGUS/SMM patients (estimated at 1/100-1/1000 person years). Although the PPVs of ALERT 20 and ALERT 20-ECG were low (<1-27.6%), the NPV was over 99% (Figure). Summary & Conclusion: Two AI-based algorithms to aid clinicians in recognizing patients with AL amyloidosis and distinguishing them from patients with MGUS/SMM are presented. These models, when tested in populations at risk of AL amyloidosis (where the prevalence of AL amyloidosis is sufficiently elevated), have a plausible PPV to be used as screening tool for this uncommon, yet life-threatening, disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outpatient Practice Pattern for Recently Approved CAR-T in Patients with Lymphoma and Multiple Myeloma

Background: FDA-approved chimeric antigen receptor T-cell (CAR-T) therapy are commonly administered in the inpatient setting given the average onset of cytokine release syndrome (CRS) is within the first 3 days post infusion. We and a few other centers have reported on the safety and feasibility of hospital-based outpatient practice (HBO) for CAR-T (Bansal et al, ASCO 2021). In Mayo Clinic Rochester practice, we have found the use of bridging therapy, elevated CRP and LDH as predictors for early hospital admission i.e., within 3 days post CAR-T infusion in patients with aggressive lymphoma (Bansal et al, ASCO 2021). Here, we report our experience with feasibility and safety of hospital-based outpatient (HBO) management of patients receiving the following CAR-T therapies: anti-BCMA CAR-Ts for multiple myeloma (MM), axicabtagene ciloleucel (axi-cel) for follicular lymphoma (FL), and brexucabtagene maraleucel (brexu-cel) for mantle cell lymphoma (MCL). Methods: We retrospectively queried a prospectively maintained database of consecutive, adult patients with MCL, FL grade 1-3A (FL1-3A) and MM who received an FDA-approved CAR-T product between 3/2021 and 6/2022 at Mayo Clinic, Rochester. Clinical course from CAR-T infusion to the time that they were dismissed home from the treatment center was reviewed. To predict baseline risk factors for admission within 72 hours of infusion, a logistic regression model was fit. Variables were selected using stepwise AIC variable selection. Results: Hospital based outpatient practice (HBO) is staffed by the same inpatient Immune Effector Cell care team, including nurses, advanced practice providers and physicians. These providers oversee patients in the hospital and HBO unit daily and provide continuity of care as patients transition between inpatient and outpatient care. HBO is the first point of contact 24/7 for patients and triage evaluations for direct inpatient admissions. The standard of care is to give lymphodepletion chemotherapy and CAR-T infusion on HBO and continue daily monitoring till day 7 and thereafter, as clinically needed until admission criteria are met. Fever, elevated CRP within 24-hour or less doubling time, or new neurologic symptoms are among the admission criteria utilized. Among 50 CAR-T recipients, 39 (78%) pts were dosed outpatient, among whom 7 (18%) were not admitted (Table 1). Median length of hospital stay for the 32 patients who were admitted was 6 days (range, 2-49). Cytokine release syndrome (CRS) and immune cell associated neurologic syndrome (ICANS) incidences for the entire cohort were comparable to that reported in registration studies. There were 2 deaths due to CAR-T related toxicity within 30 days post infusion. The median time to first admission from CAR-T infusion was 1 day (range 0-9), with 8 (25%) of admissions after 3 days. The most common cause of hospitalization was fever (25, 79%), of which 56% (14/25) were non-neutropenic. Work-up for fever was positive for infection in 4 (12.5%) patients. The median time to tocilizumab (26/32, 81%), steroid (1/31, 3%), escalation of oxygen support (4/32, 12.55), vasopressor (1/32, 3%), ventilator (1/32, 3%), hemodialysis (1/32, 3%) and ICU transfer (3/32, 9%) was 1 day (range, 0-31) after first admission. We applied the previous model (use of bridging therapy, elevated CRP and LDH) to this cohort and found this to remain correlated with early hospital admission (ROC AUC was 0.948, Figure 1). Conclusion: Our expanded study in FL, MCL and MM confirms that HBO is feasible. Axi-cel, brexu-cel, Idecabtagene vicleucel and ciltacabtagene autoleucel can be safely dosed outpatient. Approximately 20% of the patients are never admitted. In addition, variables associated with aggressive disease appear to be applicable for prediction of early hospital admission in these new CAR-T products and indications. This could potentially be used to risk stratify patients for monitoring in outpatient CAR-T practices. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal