Citations

10500 Background: Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established. Methods: We used two simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) to project lifetime breast cancer incidence and mortality in ATM, CHEK2, and PALB2 carriers. We simulated screening with annual mammography from ages 40-74 alone and with annual magnetic resonance imaging (MRI) starting at ages 40, 35, 30, and 25. Joint and separate mammography and MRI screening performance was based on published literature. Lifetime outcomes per 1,000 women were reported as means and ranges across both models. Results: Estimated risk of breast cancer by age 80 was 22% (21-23%) for ATM, 28% (26-30%) for CHEK2, and 40% (38-42%) for PALB2. Screening with MRI and mammography reduced breast cancer mortality by 52-60% across variants (Table). Compared to no screening, starting MRI at age 30 increased life years (LY)/1000 women by 501 (478-523) in ATM, 620 (587-652) in CHEK2, and 1,025 (998-1,051) in PALB2. Starting MRI at age 25 versus 30 gained 9-12 LY/1000 women with 517-518 additional false positive screens and 197-198 benign biopsies. Conclusions: For women with ATM, CHEK2, and PALB2 pathogenic variants, breast cancer screening with MRI and mammography halves breast cancer mortality. These mortality benefits are similar to those for MRI screening for BRCA1/2 mutation carriers and should inform practice guidelines.[Table: see text]

e19552 Background: Leukemic involvement (LI) in diffuse large B cell lymphoma (L-DLBCL) is very rare and has been sparsely reported. We report our experience with this entity in a large academic multi-center setting. Methods: Medical records of patients with DLBCL who received care at Mayo Clinic between 1/2003 and 6/2020 were reviewed. DLBCL patients with LI were identified. LI was defined as increased white blood cell counts and the presence of clonal B cells on peripheral blood flow-cytometry. Kaplan-Meier method was used for survival analysis. Results: Twenty patients with L-DLBCL were identified with a median follow-up of 32.5 months (CI95%, 32.5-NR). Median age at initial diagnosis was 62 (45-80) years. 60% (12/20) were male; 90% (18/20) were Caucasian. Pathologically, 90% (18/20) had DLBCL and 10% (2/20) had high-grade B cell lymphoma (HGBCL) with intermediate features between DLBCL and Burkitt lymphoma. By Hans criteria, 58% (11/19) had germinal center B-cell DLBCL (GCB-DLBCL) and 42% (8/19) had non-germinal center B-cell DLBCL (non-GCB-DLBCL). 40% (8/20) had transformed DLBCL (t-DLBCL); 36% (5/14) had double-hit lymphoma (DHL) by FISH analysis. LI was present in 55% (11/20) at initial diagnosis and 45% (9/20) at relapse. Median WBC was 39.5/ul (range, 4.3-121) with median absolute lymphocyte count of 25 k/ul (range, 0.7-117). Immunophenotypically, the leukemic lymphoma cells expressed CD19, CD20, and CD79a. Bone marrow involvement and pancytopenia were documented in all patients with a median bone marrow cellularity of 80%. Other extranodal sites of involvement with LI included spleen (65%;13/20), liver (20%;4/20), breast and soft tissue (20%;4/20), bladder or kidneys (10%;2/20), skeleton (10%;2/20), and myocardium (5%;1/20). 65% (13/20) had B-symptoms. All patients had LDH elevation (UNL 222 U/L) with a median of 2125 U/L (range, 308-10,760). 45% (5/11) of patients with LI at initial diagnosis had CNS involvement on relapse/progression. All patients with LI at initial diagnosis received anthracycline-based chemoimmunotherapy with or without CNS prophylaxis. Patients with LI at relapse had had a median of 2 prior treatments (range, 1-5) before LI. Median overall survival (OS) for the whole group was 9 months (CI 95%; 5.8-11.8). There were no long-term survivors. Median progression free survival after LI was 4.7 months (CI95%; 0.8-7.6) in the newly diagnosed group and 3 months (CI95%; 0.9-20) in the relapsed group. 90% (18/20) died due to their progressive disease. Cell of origin, DHL status, or newly diagnosed vs. relapsed status did not have a significant impact on OS in patients with L-DLBCL. Conclusions: Leukemic involvement at any time during the course of DLBCL is associated with poor prognosis. It also appears to be a major risk factor for CNS relapse. It is most frequently associated with DHL and t-DLBCL. Novel therapeutic approaches at the time of initial therapy need to be developed for L-DLBCL.

e19501 Background: The current standard of care for patients with relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) following frontline immunochemotherapy (IC) is salvage therapy, followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) rescue in patients responding to salvage therapy. Time to first relapse (or refractory status) and response to salvage therapy in patients with RR DLBCL may reflect the chemosensitivity of the underlying disease. The aim of this study is to determine whether these factors impact post-ASCT outcomes. Methods: Patients with DLBCL that relapsed after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Results: A total of 437 patients with RR DLBCL who underwent salvage therapy and ASCT were identified. 280 (64%) were male. Median time from initial diagnosis to 1st relapse/salvage was 1.0 years (range 0.1-16.4). A median of 1 line (range 1-3) of salvage therapy was required. Response prior to ASCT was complete response (CR) in 211 (48%), partial response in 199 (46%), stable disease in 24 (5%), and unknown in 3 (1%) patients. Median age at ASCT was 61 years (range 19-78), and median follow up after ASCT was 8.0 years (95% CI 7.2-8.7). Median PFS and OS was 2.7 (95% CI 1.5-4.3) and 5.4 (4.2-7.4) years, respectively. Time to 1st relapse/salvage (≤1 vs 1-2 vs > 2 years) was not associated with PFS (median 0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs 7.4 vs 6.8 years, p = 0.013). Patients who required > 1 line of salvage therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p < 0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who failed to achieve a CR prior to ASCT had significantly worse PFS (median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p < 0.001). In multivariate Cox regression models adjusted for age and sex, time to 1st relapse/salvage was not associated with PFS (p = 0.313) or OS (p = 0.081); however, lines of salvage and response prior to ASCT remain significantly prognostic for PFS ( > 1 line of salvage: HR 2.14, 95% CI 1.59-2.87, p < 0.001; non-CR: HR 1.61, 95% CI 1.26-2.05, p < 0.001) and OS ( > 1 line of salvage: HR 2.25, 95% CI 1.66-3.05, p < 0.001; non-CR: HR 1.63, 95% CI 1.26-2.12, p < 0.001). Conclusions: In patients with RR DLBCL following frontline IC, requiring more than 1 line of salvage therapy and failure to achieve CR are strong independent risk factors for poor PFS and OS after ASCT. Novel therapies such as CAR-T cell therapy should be studied in this population.

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( > 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p < 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]

6539 Background: The impact of insurance status on survival in diffuse large B‐cell lymphoma (DLBCL), the most common aggressive lymphoma, has not been evaluated after the implementation of the Affordable Care Act (ACA). The aim of this study is to compare overall survival (OS) in patients across insurance status groups and in the periods before and after the ACA. Methods: Adult patients with newly diagnosed DLBCL were identified from the National Cancer Database. The analysis was restricted to patients 64 years of age or younger as most patients 65 years or older are eligible for Medicare under the ACA. The 2004-2017 period was chosen to represent the immunochemotherapy era preceding and following the ACA. Logistic regression was used to explore associations between abstracted variables and insurance status groups. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: 93,692 adults (age < 64 years) with newly diagnosed DLBCL and known insurance status were identified (41.3% female, median age 54 years [range: 18 – 64], 81.8% White and 12.1% Black). 7,211 (7.7%) patients were uninsured, 64,744 (69.1%) had private insurance, 11,936 (12.7%) had Medicaid, and 9,801 (10.5%) had Medicare. When compared to insured patients (private insurance, Medicaid or Medicare), uninsured patients were more likely to have a median household outcome of < $38,000 [OR 1.93 (95% CI 1.79-2.07)], less likely to receive chemotherapy [OR 0.69 (0.64-0.77)], more likely to be male [OR 1.14 (1.07-1.21)], more likely to be non-White [OR 1.30 (1.20-1.40], and more likely to present with stage III or IV disease [OR 1.24 (1.16-1.32)]. Uninsured patients had an inferior OS [HR 1.21 (95% CI 1.15-1.27)] when compared to insured patients after adjustment for baseline comorbidity (Charlson-Deyo score ≥2), advanced stage, treatment with chemotherapy, and sociodemographic factors including sex, age, race, household income, facility type (academic/community), and location (urban/rural). With a median follow-up time of 14.8 years (95% CI 14.6-not reached), median OS was lower in uninsured patients [13.4 years (12.3-not reached) vs 14.8 years (14.7-not reached); p < 0.0001]. Despite the lack of major changes in DLBCL therapies, a diagnosis after the implementation of the ACA (in 2010 or later) was associated with a superior OS when compared with the outcomes of patients diagnosed in 2010 or earlier [HR 0.93 (95% CI 0.90-0.95)]. Similarly, five-year OS was superior in the insured group [HR 0.93 (95% CI 0.89-0.96)]. Conclusions: Uninsured patients with DLBCL and < 64 years old had inferior OS when compared with insured patients, and uninsured status emerged as an independent risk factor for inferior OS. Our data highlight the independent effect of insurance disparities - a potential indicator of variations in access to health care - on survival in DLBCL.

BACKGROUND: Peak flow testing is a common procedure performed in ambulatory care. There are currently no data regarding aerosol generation during this procedure. Given the ongoing debate regarding the potential for aerosol transmission of SARS-CoV-2, we aimed to quantify and characterize aerosol generation during peak flow testing. METHODS: Five healthy volunteers performed peak flow maneuvers in a particle-free laboratory space. Two devices continuously sampled the ambient air during the procedure. One device can detect ultrafine particles 0.02–1 μ m in diameter, while the second device can detect particles 0.3, 0.5, 1.0, 2.0, 5.0, and 10 μ m in diameter. Five different peak flow meters were compared to ambient baseline during masked and unmasked tidal breathing. RESULTS: Ultrafine particles (0.02–1 μ m) were generated during peak flow measurement. There was no significant difference in ultrafine particle mean concentration between peak flow meters ( P = .23): Respironics (1.25 ± 0.47 particles/mL), Philips (3.06 ± 1.22), Clement Clarke (3.55 ± 1.22 particles/mL), Respironics Low Range (3.50 ± 1.52 particles/mL), and Monaghan (3.78 ± 1.31 particles/mL). Ultrafine particle mean concentration with peak flow testing was significantly higher than masked (0.22 ± 0.29 particles/mL) and unmasked tidal breathing (0.15 ± 0.18 particles/mL, P = .01), but the ultrafine particle concentrations were small compared to ambient particle concentrations in a pulmonary function testing room (89.9 ± 8.95 particles/mL). CONCLUSIONS: In this study, aerosol generation was present during peak flow testing, but concentrations were small compared to the background particle concentration in the ambient clinical environment. Surgical masks and eye protection are likely sufficient infection control measures during peak expiratory flow testing in asymptomatic patients with well controlled respiratory symptoms, but COVID-19 testing remains prudent in patients with acute respiratory symptoms prior to evaluation and peak expiratory flow assessment while the community prevalence of SARS-CoV-2 cases remains high.

Abstract Self‐affirmation interventions have been shown to mitigate the negative psychological effects of stereotype threat on Black students in secondary and undergraduate education. However, there is currently limited research testing whether Black students in medical schools may also experience the negative influences of stereotype threat. Until now, it has been unclear whether Black (vs. White) students experience a lower sense of belonging in medical school and whether they can benefit from self‐affirmation interventions during medical training. With a longitudinal field experiment, we tested (a) whether Black (vs. White) medical students in the US experience decrements in psychological well‐being (i.e., fatigue, depression, anxiety), sense of belonging, perceived residency competitiveness, and residency goal stability; and (b) the extent to which a self‐affirmation intervention would ameliorate any observed disparities in these outcomes for Black students. With a sample of 234 Black and 182 White medical students across 50 schools in the United States, we found that Black students tended to report more fatigue and less belonging than White students; however, the self‐affirmation intervention did not significantly influence students’ fatigue, depression, anxiety, or belonging. Unexpectedly, Black students in the self‐affirmation (vs. control) condition reported lower perceived competitiveness for residency. White students’ perceived competitiveness for residency was unaffected by the intervention. Exploratory analyses revealed that Black (vs. White) students were less likely to indicate stable residency goals over time, which may be an indication of threat; however, this racial gap was eliminated with the intervention. We discuss the plausible reasons for these findings and provide recommendations for future work in this area.